|
|
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result sql = Apoptosis of cerebellar granule cells induced by organotin compounds found in drinking water: involvement of MAP kinases.
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char = y;code = 121
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = E;code = 69
char = C;code = 67
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char = 5;code = 53
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char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = 3;code = 51
char = ;code = 32
char = m;code = 109
char = i;code = 105
char = c;code = 99
char = r;code = 114
char = o;code = 111
char = M;code = 77
char = .;code = 46
char = ;code = 32
char = E;code = 69
char = x;code = 120
char = p;code = 112
char = o;code = 111
char = s;code = 115
char = u;code = 117
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = t;code = 116
char = o;code = 111
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char = M;code = 77
char = M;code = 77
char = T;code = 84
char = ,;code = 44
char = ;code = 32
char = D;code = 68
char = M;code = 77
char = T;code = 84
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = M;code = 77
char = B;code = 66
char = T;code = 84
char = ;code = 32
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = s;code = 115
char = ;code = 32
char = u;code = 117
char = p;code = 112
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = 1;code = 49
char = 0;code = 48
char = ;code = 32
char = m;code = 109
char = i;code = 105
char = c;code = 99
char = r;code = 114
char = o;code = 111
char = M;code = 77
char = ;code = 32
char = h;code = 104
char = a;code = 97
char = d;code = 100
char = ;code = 32
char = n;code = 110
char = o;code = 111
char = ;code = 32
char = e;code = 101
char = f;code = 102
char = f;code = 102
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = .;code = 46
char = ;code = 32
char = D;code = 68
char = B;code = 66
char = T;code = 84
char = ,;code = 44
char = ;code = 32
char = h;code = 104
char = o;code = 111
char = w;code = 119
char = e;code = 101
char = v;code = 118
char = e;code = 101
char = r;code = 114
char = ,;code = 44
char = ;code = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = v;code = 118
char = e;code = 101
char = r;code = 114
char = y;code = 121
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char = p;code = 112
char = o;code = 111
char = t;code = 116
char = e;code = 101
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char = t;code = 116
char = ,;code = 44
char = ;code = 32
char = a;code = 97
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char = d;code = 100
char = ;code = 32
char = d;code = 100
char = e;code = 101
char = c;code = 99
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = ;code = 32
char = v;code = 118
char = i;code = 105
char = a;code = 97
char = b;code = 98
char = i;code = 105
char = l;code = 108
char = i;code = 105
char = t;code = 116
char = y;code = 121
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = E;code = 69
char = C;code = 67
char = (;code = 40
char = 5;code = 53
char = 0;code = 48
char = );code = 41
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = 0;code = 48
char = .;code = 46
char = 3;code = 51
char = ;code = 32
char = m;code = 109
char = i;code = 105
char = c;code = 99
char = r;code = 114
char = o;code = 111
char = M;code = 77
char = .;code = 46
char = ;code = 32
char = S;code = 83
char = t;code = 116
char = a;code = 97
char = i;code = 105
char = n;code = 110
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = o;code = 111
char = r;code = 114
char = g;code = 103
char = a;code = 97
char = n;code = 110
char = o;code = 111
char = t;code = 116
char = i;code = 105
char = n;code = 110
char = -;code = 45
char = t;code = 116
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = c;code = 99
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = b;code = 98
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = a;code = 97
char = r;code = 114
char = ;code = 32
char = g;code = 103
char = r;code = 114
char = a;code = 97
char = n;code = 110
char = u;code = 117
char = l;code = 108
char = e;code = 101
char = ;code = 32
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = s;code = 115
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = n;code = 110
char = u;code = 117
char = c;code = 99
char = l;code = 108
char = e;code = 101
char = a;code = 97
char = r;code = 114
char = ;code = 32
char = d;code = 100
char = y;code = 121
char = e;code = 101
char = ;code = 32
char = S;code = 83
char = y;code = 121
char = t;code = 116
char = o;code = 111
char = -;code = 45
char = 1;code = 49
char = 3;code = 51
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = v;code = 118
char = e;code = 101
char = a;code = 97
char = l;code = 108
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = T;code = 84
char = M;code = 77
char = T;code = 84
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = D;code = 68
char = B;code = 66
char = T;code = 84
char = ,;code = 44
char = ;code = 32
char = b;code = 98
char = u;code = 117
char = t;code = 116
char = ;code = 32
char = n;code = 110
char = o;code = 111
char = t;code = 116
char = ;code = 32
char = M;code = 77
char = M;code = 77
char = T;code = 84
char = ,;code = 44
char = ;code = 32
char = D;code = 68
char = M;code = 77
char = T;code = 84
char = ,;code = 44
char = ;code = 32
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = M;code = 77
char = B;code = 66
char = T;code = 84
char = ,;code = 44
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = d;code = 100
char = u;code = 117
char = c;code = 99
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = n;code = 110
char = d;code = 100
char = e;code = 101
char = n;code = 110
char = s;code = 115
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = f;code = 102
char = r;code = 114
char = a;code = 97
char = g;code = 103
char = m;code = 109
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = c;code = 99
char = h;code = 104
char = r;code = 114
char = o;code = 111
char = m;code = 109
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = c;code = 99
char = h;code = 104
char = a;code = 97
char = r;code = 114
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = i;code = 105
char = s;code = 115
char = t;code = 116
char = i;code = 105
char = c;code = 99
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char = o;code = 111
char = f;code = 102
char = ;code = 32
char = a;code = 97
char = p;code = 112
char = o;code = 111
char = p;code = 112
char = t;code = 116
char = o;code = 111
char = s;code = 115
char = i;code = 105
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = T;code = 84
char = M;code = 77
char = T;code = 84
char = -;code = 45
char = ;code = 32
char = a;code = 97
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char = d;code = 100
char = ;code = 32
char = D;code = 68
char = B;code = 66
char = T;code = 84
char = -;code = 45
char = i;code = 105
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char = d;code = 100
char = u;code = 117
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char = e;code = 101
char = d;code = 100
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char = a;code = 97
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char = o;code = 111
char = p;code = 112
char = t;code = 116
char = o;code = 111
char = s;code = 115
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = n;code = 110
char = f;code = 102
char = i;code = 105
char = r;code = 114
char = m;code = 109
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = u;code = 117
char = s;code = 115
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = T;code = 84
char = U;code = 85
char = N;code = 78
char = E;code = 69
char = L;code = 76
char = ;code = 32
char = s;code = 115
char = t;code = 116
char = a;code = 97
char = i;code = 105
char = n;code = 110
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = a;code = 97
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char = d;code = 100
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char = m;code = 109
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = u;code = 117
char = r;code = 114
char = e;code = 101
char = m;code = 109
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = P;code = 80
char = A;code = 65
char = R;code = 82
char = P;code = 80
char = ;code = 32
char = c;code = 99
char = l;code = 108
char = e;code = 101
char = a;code = 97
char = v;code = 118
char = a;code = 97
char = g;code = 103
char = e;code = 101
char = .;code = 46
char = ;code = 32
char = A;code = 65
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
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char = o;code = 111
char = f;code = 102
char = ;code = 32
char = M;code = 77
char = A;code = 65
char = P;code = 80
char = ;code = 32
char = k;code = 107
char = i;code = 105
char = n;code = 110
char = a;code = 97
char = s;code = 115
char = e;code = 101
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char = p;code = 112
char = a;code = 97
char = t;code = 116
char = h;code = 104
char = w;code = 119
char = a;code = 97
char = y;code = 121
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char = a;code = 97
char = s;code = 115
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char = e;code = 101
char = x;code = 120
char = a;code = 97
char = m;code = 109
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char = e;code = 101
char = d;code = 100
char = ;code = 32
char = a;code = 97
char = f;code = 102
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = 6;code = 54
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char = h;code = 104
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = e;code = 101
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char = p;code = 112
char = o;code = 111
char = s;code = 115
char = u;code = 117
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
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char = o;code = 111
char = r;code = 114
char = g;code = 103
char = a;code = 97
char = n;code = 110
char = o;code = 111
char = t;code = 116
char = i;code = 105
char = n;code = 110
char = s;code = 115
char = ;code = 32
char = w;code = 119
char = h;code = 104
char = i;code = 105
char = c;code = 99
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char = ;code = 32
char = i;code = 105
char = n;code = 110
char = d;code = 100
char = u;code = 117
char = c;code = 99
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = a;code = 97
char = p;code = 112
char = o;code = 111
char = p;code = 112
char = t;code = 116
char = o;code = 111
char = s;code = 115
char = i;code = 105
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = B;code = 66
char = o;code = 111
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = T;code = 84
char = M;code = 77
char = T;code = 84
char = ;code = 32
char = a;code = 97
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char = d;code = 100
char = ;code = 32
char = D;code = 68
char = B;code = 66
char = T;code = 84
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = E;code = 69
char = R;code = 82
char = K;code = 75
char = 1;code = 49
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char = 2;code = 50
char = ,;code = 44
char = ;code = 32
char = b;code = 98
char = u;code = 117
char = t;code = 116
char = ;code = 32
char = o;code = 111
char = n;code = 110
char = l;code = 108
char = y;code = 121
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char = T;code = 84
char = M;code = 77
char = T;code = 84
char = ;code = 32
char = a;code = 97
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char = e;code = 101
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char = J;code = 74
char = N;code = 78
char = K;code = 75
char = /;code = 47
char = c;code = 99
char = -;code = 45
char = J;code = 74
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char = a;code = 97
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char = h;code = 104
char = w;code = 119
char = a;code = 97
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char = P;code = 80
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char = a;code = 97
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char = d;code = 100
char = e;code = 101
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char = o;code = 111
char = f;code = 102
char = ;code = 32
char = J;code = 74
char = N;code = 78
char = K;code = 75
char = /;code = 47
char = c;code = 99
char = -;code = 45
char = J;code = 74
char = u;code = 117
char = n;code = 110
char = ;code = 32
char = a;code = 97
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char = d;code = 100
char = ;code = 32
char = p;code = 112
char = 3;code = 51
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char = ;code = 32
char = a;code = 97
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char = t;code = 116
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char = v;code = 118
char = a;code = 97
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char = o;code = 111
char = n;code = 110
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char = s;code = 115
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char = i;code = 105
char = c;code = 99
char = a;code = 97
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char = d;code = 100
char = e;code = 101
char = c;code = 99
char = r;code = 114
char = e;code = 101
char = a;code = 97
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char = e;code = 101
char = d;code = 100
char = ;code = 32
char = a;code = 97
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char = o;code = 111
char = p;code = 112
char = t;code = 116
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char = i;code = 105
char = s;code = 115
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char = u;code = 117
char = c;code = 99
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = b;code = 98
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char = T;code = 84
char = M;code = 77
char = T;code = 84
char = ,;code = 44
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char = b;code = 98
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char = t;code = 116
char = ;code = 32
char = n;code = 110
char = o;code = 111
char = t;code = 116
char = ;code = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = D;code = 68
char = B;code = 66
char = T;code = 84
char = .;code = 46
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char = T;code = 84
char = h;code = 104
char = e;code = 101
char = s;code = 115
char = e;code = 101
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char = s;code = 115
char = u;code = 117
char = l;code = 108
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = s;code = 115
char = h;code = 104
char = o;code = 111
char = w;code = 119
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char = t;code = 116
char = h;code = 104
char = a;code = 97
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char = ;code = 32
char = D;code = 68
char = B;code = 66
char = T;code = 84
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char = i;code = 105
char = s;code = 115
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char = a;code = 97
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char = p;code = 112
char = o;code = 111
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char = e;code = 101
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char = u;code = 117
char = r;code = 114
char = o;code = 111
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char = o;code = 111
char = x;code = 120
char = i;code = 105
char = c;code = 99
char = a;code = 97
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char = t;code = 116
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char = i;code = 105
char = n;code = 110
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char = v;code = 118
char = i;code = 105
char = t;code = 116
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char = ,;code = 44
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char = b;code = 98
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char = t;code = 116
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char = u;code = 117
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char = l;code = 108
char = i;code = 105
char = k;code = 107
char = e;code = 101
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char = T;code = 84
char = M;code = 77
char = T;code = 84
char = ,;code = 44
char = ;code = 32
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result sql = Mono- and dialkyl organotin compounds are used primarily as heat stabilizers in polyvinyl chloride (PVC) plastics. Recently, monomethyltin (MMT), dimethyltin (DMT), monobutyltin (MBT), and dibutyltin (DBT) have been detected in water from homes and businesses served by PVC pipes. While trialkyl organotins such as trimethyltin (TMT) and triethyltin (TET) are well known neurotoxicants, the toxicity of the mono- and dialkyl organotins is not well described. The present study compared the cytotoxicity of organotins found in drinking water with the known neurotoxicant TMT in primary cultures of cerebellar granule cells, and examined the role of MAP kinase signaling in organotin-induced cell death. Twenty-four hour exposure to TMT resulted in a concentration-dependent decrease in cell viability with an EC(50) of 3 microM. Exposure to MMT, DMT, and MBT at concentrations up to 10 microM had no effect. DBT, however, was very potent, and decreased cell viability with an EC(50) of 0.3 microM. Staining of organotin-treated cerebellar granule cells with the nuclear dye Syto-13 revealed that TMT and DBT, but not MMT, DMT, or MBT, produced condensation and fragmentation of chromatin characteristic of apoptosis. TMT- and DBT-induced apoptosis was confirmed using TUNEL staining and measurement of PARP cleavage. Activation of MAP kinase pathways was examined after 6 h of exposure to the organotins which induced apoptosis. Both TMT and DBT activated ERK1/2, but only TMT activated the JNK/c-Jun and p38 pathways. Pharmacologic blockade of JNK/c-Jun and p38 activation significantly decreased apoptosis produced by TMT, but not by DBT. These results show that DBT is a potent neurotoxicant in vitro, but unlike TMT, does not induce cell death via activation of MAP kinase signaling.
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result sql = Apoptosis of cerebellar granule cells induced by organotin compounds found in drinking water: involvement of MAP kinases.
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char = l;code = 108
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char = T;code = 84
char = w;code = 119
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = y;code = 121
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char = u;code = 117
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char = r;code = 114
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char = t;code = 116
char = o;code = 111
char = ;code = 32
char = T;code = 84
char = M;code = 77
char = T;code = 84
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char = r;code = 114
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char = s;code = 115
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char = t;code = 116
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char = t;code = 116
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char = c;code = 99
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char = l;code = 108
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char = t;code = 116
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char = E;code = 69
char = C;code = 67
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char = s;code = 115
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char = r;code = 114
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char = t;code = 116
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char = M;code = 77
char = M;code = 77
char = T;code = 84
char = ,;code = 44
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char = D;code = 68
char = M;code = 77
char = T;code = 84
char = ,;code = 44
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char = a;code = 97
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char = d;code = 100
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char = M;code = 77
char = B;code = 66
char = T;code = 84
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char = a;code = 97
char = t;code = 116
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char = c;code = 99
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char = n;code = 110
char = c;code = 99
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char = n;code = 110
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char = a;code = 97
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char = i;code = 105
char = o;code = 111
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char = s;code = 115
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char = u;code = 117
char = p;code = 112
char = ;code = 32
char = t;code = 116
char = o;code = 111
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char = 1;code = 49
char = 0;code = 48
char = ;code = 32
char = m;code = 109
char = i;code = 105
char = c;code = 99
char = r;code = 114
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char = M;code = 77
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char = h;code = 104
char = a;code = 97
char = d;code = 100
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char = o;code = 111
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char = e;code = 101
char = f;code = 102
char = f;code = 102
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = .;code = 46
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char = D;code = 68
char = B;code = 66
char = T;code = 84
char = ,;code = 44
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char = h;code = 104
char = o;code = 111
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char = e;code = 101
char = v;code = 118
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char = r;code = 114
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char = w;code = 119
char = a;code = 97
char = s;code = 115
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char = v;code = 118
char = e;code = 101
char = r;code = 114
char = y;code = 121
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char = p;code = 112
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char = t;code = 116
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char = ;code = 32
char = a;code = 97
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char = d;code = 100
char = e;code = 101
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char = r;code = 114
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char = a;code = 97
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char = e;code = 101
char = d;code = 100
char = ;code = 32
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
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char = v;code = 118
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char = a;code = 97
char = b;code = 98
char = i;code = 105
char = l;code = 108
char = i;code = 105
char = t;code = 116
char = y;code = 121
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char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = a;code = 97
char = n;code = 110
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char = E;code = 69
char = C;code = 67
char = (;code = 40
char = 5;code = 53
char = 0;code = 48
char = );code = 41
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = 0;code = 48
char = .;code = 46
char = 3;code = 51
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char = m;code = 109
char = i;code = 105
char = c;code = 99
char = r;code = 114
char = o;code = 111
char = M;code = 77
char = .;code = 46
char = ;code = 32
char = S;code = 83
char = t;code = 116
char = a;code = 97
char = i;code = 105
char = n;code = 110
char = i;code = 105
char = n;code = 110
char = g;code = 103
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char = o;code = 111
char = f;code = 102
char = ;code = 32
char = o;code = 111
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char = a;code = 97
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char = o;code = 111
char = t;code = 116
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char = n;code = 110
char = -;code = 45
char = t;code = 116
char = r;code = 114
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char = a;code = 97
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char = e;code = 101
char = d;code = 100
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char = e;code = 101
char = b;code = 98
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = a;code = 97
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char = g;code = 103
char = r;code = 114
char = a;code = 97
char = n;code = 110
char = u;code = 117
char = l;code = 108
char = e;code = 101
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char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = s;code = 115
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char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
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char = t;code = 116
char = h;code = 104
char = e;code = 101
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char = l;code = 108
char = e;code = 101
char = a;code = 97
char = r;code = 114
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char = d;code = 100
char = y;code = 121
char = e;code = 101
char = ;code = 32
char = S;code = 83
char = y;code = 121
char = t;code = 116
char = o;code = 111
char = -;code = 45
char = 1;code = 49
char = 3;code = 51
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char = r;code = 114
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char = v;code = 118
char = e;code = 101
char = a;code = 97
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char = h;code = 104
char = a;code = 97
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char = T;code = 84
char = M;code = 77
char = T;code = 84
char = ;code = 32
char = a;code = 97
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char = D;code = 68
char = B;code = 66
char = T;code = 84
char = ,;code = 44
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char = b;code = 98
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char = t;code = 116
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char = M;code = 77
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char = D;code = 68
char = M;code = 77
char = T;code = 84
char = ,;code = 44
char = ;code = 32
char = o;code = 111
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char = M;code = 77
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char = T;code = 84
char = ,;code = 44
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char = p;code = 112
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char = o;code = 111
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char = i;code = 105
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = T;code = 84
char = M;code = 77
char = T;code = 84
char = -;code = 45
char = ;code = 32
char = a;code = 97
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char = D;code = 68
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char = T;code = 84
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char = u;code = 117
char = s;code = 115
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = T;code = 84
char = U;code = 85
char = N;code = 78
char = E;code = 69
char = L;code = 76
char = ;code = 32
char = s;code = 115
char = t;code = 116
char = a;code = 97
char = i;code = 105
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char = n;code = 110
char = g;code = 103
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char = a;code = 97
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char = a;code = 97
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char = r;code = 114
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char = m;code = 109
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char = n;code = 110
char = t;code = 116
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char = o;code = 111
char = f;code = 102
char = ;code = 32
char = P;code = 80
char = A;code = 65
char = R;code = 82
char = P;code = 80
char = ;code = 32
char = c;code = 99
char = l;code = 108
char = e;code = 101
char = a;code = 97
char = v;code = 118
char = a;code = 97
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char = e;code = 101
char = .;code = 46
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char = c;code = 99
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char = a;code = 97
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char = i;code = 105
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char = M;code = 77
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char = k;code = 107
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char = n;code = 110
char = a;code = 97
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char = a;code = 97
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char = a;code = 97
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char = M;code = 77
char = T;code = 84
char = ;code = 32
char = a;code = 97
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char = D;code = 68
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char = v;code = 118
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char = e;code = 101
char = d;code = 100
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char = E;code = 69
char = R;code = 82
char = K;code = 75
char = 1;code = 49
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char = 2;code = 50
char = ,;code = 44
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char = b;code = 98
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char = o;code = 111
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char = l;code = 108
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char = T;code = 84
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char = a;code = 97
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char = d;code = 100
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char = e;code = 101
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char = J;code = 74
char = N;code = 78
char = K;code = 75
char = /;code = 47
char = c;code = 99
char = -;code = 45
char = J;code = 74
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char = w;code = 119
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char = P;code = 80
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char = a;code = 97
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char = e;code = 101
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char = o;code = 111
char = f;code = 102
char = ;code = 32
char = J;code = 74
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char = K;code = 75
char = /;code = 47
char = c;code = 99
char = -;code = 45
char = J;code = 74
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char = n;code = 110
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char = a;code = 97
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char = p;code = 112
char = 3;code = 51
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char = v;code = 118
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char = f;code = 102
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char = a;code = 97
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char = d;code = 100
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char = o;code = 111
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char = t;code = 116
char = o;code = 111
char = s;code = 115
char = i;code = 105
char = s;code = 115
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result sql = Mono- and dialkyl organotin compounds are used primarily as heat stabilizers in polyvinyl chloride (PVC) plastics. Recently, monomethyltin (MMT), dimethyltin (DMT), monobutyltin (MBT), and dibutyltin (DBT) have been detected in water from homes and businesses served by PVC pipes. While trialkyl organotins such as trimethyltin (TMT) and triethyltin (TET) are well known neurotoxicants, the toxicity of the mono- and dialkyl organotins is not well described. The present study compared the cytotoxicity of organotins found in drinking water with the known neurotoxicant TMT in primary cultures of cerebellar granule cells, and examined the role of MAP kinase signaling in organotin-induced cell death. Twenty-four hour exposure to TMT resulted in a concentration-dependent decrease in cell viability with an EC(50) of 3 microM. Exposure to MMT, DMT, and MBT at concentrations up to 10 microM had no effect. DBT, however, was very potent, and decreased cell viability with an EC(50) of 0.3 microM. Staining of organotin-treated cerebellar granule cells with the nuclear dye Syto-13 revealed that TMT and DBT, but not MMT, DMT, or MBT, produced condensation and fragmentation of chromatin characteristic of apoptosis. TMT- and DBT-induced apoptosis was confirmed using TUNEL staining and measurement of PARP cleavage. Activation of MAP kinase pathways was examined after 6 h of exposure to the organotins which induced apoptosis. Both TMT and DBT activated ERK1/2, but only TMT activated the JNK/c-Jun and p38 pathways. Pharmacologic blockade of JNK/c-Jun and p38 activation significantly decreased apoptosis produced by TMT, but not by DBT. These results show that DBT is a potent neurotoxicant in vitro, but unlike TMT, does not induce cell death via activation of MAP kinase signaling.
Publication: Neurotoxicology 2006 Jan ;27(1)::71-81.
Publication Date: 2006 Jan
Study Author(s): Mundy, William R;Freudenrich, Theresa M;
Institution: National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, B105-06, Research Triangle Park, NC 27711, USA. [email protected]
Shortcut link to this study:
Publication Date: 2006 Jan
Study Author(s): Mundy, William R;Freudenrich, Theresa M;
Institution: National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, B105-06, Research Triangle Park, NC 27711, USA. [email protected]
Shortcut link to this study:
Mono- and dialkyl organotin compounds are used primarily as heat stabilizers in polyvinyl chloride (PVC) plastics. Recently, monomethyltin (MMT), dimethyltin (DMT), monobutyltin (MBT), and dibutyltin (DBT) have been detected in water from homes and businesses served by PVC pipes. While trialkyl organotins such as trimethyltin (TMT) and triethyltin (TET) are well known neurotoxicants, the toxicity of the mono- and dialkyl organotins is not well described. The present study compared the cytotoxicity of organotins found in drinking water with the known neurotoxicant TMT in primary cultures of cerebellar granule cells, and examined the role of MAP kinase signaling in organotin-induced cell death. Twenty-four hour exposure to TMT resulted in a concentration-dependent decrease in cell viability with an EC(50) of 3 microM. Exposure to MMT, DMT, and MBT at concentrations up to 10 microM had no effect. DBT, however, was very potent, and decreased cell viability with an EC(50) of 0.3 microM. Staining of organotin-treated cerebellar granule cells with the nuclear dye Syto-13 revealed that TMT and DBT, but not MMT, DMT, or MBT, produced condensation and fragmentation of chromatin characteristic of apoptosis. TMT- and DBT-induced apoptosis was confirmed using TUNEL staining and measurement of PARP cleavage. Activation of MAP kinase pathways was examined after 6 h of exposure to the organotins which induced apoptosis. Both TMT and DBT activated ERK1/2, but only TMT activated the JNK/c-Jun and p38 pathways. Pharmacologic blockade of JNK/c-Jun and p38 activation significantly decreased apoptosis produced by TMT, but not by DBT. These results show that DBT is a potent neurotoxicant in vitro, but unlike TMT, does not induce cell death via activation of MAP kinase signaling.
PMID: 16181675
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