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char = l;code = 108
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char = l;code = 108
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char = o;code = 111
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char = c;code = 99
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char = c;code = 99
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char = l;code = 108
char = l;code = 108
char = s;code = 115
char = .;code = 46
result sql = Effect of glutathione depletion on inhibition of cell cycle progression and induction of apoptosis by melphalan (L-phenylalanine mustard) in human colorectal cancer cells.
Effect of glutathione depletion on inhibition of cell cycle progression and induction of apoptosis by melphalan (L-phenylalanine mustard) in human colorectal cancer cells.
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char = e;code = 101
char = s;code = 115
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char = o;code = 111
char = f;code = 102
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
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char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
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char = c;code = 99
char = y;code = 121
char = c;code = 99
char = l;code = 108
char = e;code = 101
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char = ;code = 32
char = Y;code = 89
char = e;code = 101
char = t;code = 116
char = ,;code = 44
char = ;code = 32
char = B;code = 66
char = S;code = 83
char = O;code = 79
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = t;code = 116
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = t;code = 116
char = m;code = 109
char = e;code = 101
char = n;code = 110
char = t;code = 116
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char = d;code = 100
char = i;code = 105
char = d;code = 100
char = ;code = 32
char = n;code = 110
char = o;code = 111
char = t;code = 116
char = ;code = 32
char = a;code = 97
char = f;code = 102
char = f;code = 102
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = u;code = 117
char = l;code = 108
char = a;code = 97
char = r;code = 114
char = ;code = 32
char = L;code = 76
char = -;code = 45
char = P;code = 80
char = A;code = 65
char = M;code = 77
char = ;code = 32
char = c;code = 99
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char = n;code = 110
char = t;code = 116
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = <;code = 60
char = b;code = 98
char = >;code = 62
char = ;code = 32
char = L;code = 76
char = -;code = 45
char = P;code = 80
char = A;code = 65
char = M;code = 77
char = ;code = 32
char = :;code = 58
char = ;code = 32
char = <;code = 60
char = /;code = 47
char = b;code = 98
char = >;code = 62
char = i;code = 105
char = n;code = 110
char = d;code = 100
char = u;code = 117
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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
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char = i;code = 105
char = n;code = 110
char = ;code = 32
char = b;code = 98
char = o;code = 111
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = n;code = 110
char = o;code = 111
char = r;code = 114
char = m;code = 109
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = G;code = 71
char = S;code = 83
char = H;code = 72
char = -;code = 45
char = d;code = 100
char = e;code = 101
char = p;code = 112
char = l;code = 108
char = e;code = 101
char = t;code = 116
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 = s;code = 115
char = .;code = 46
char = ;code = 32
char = A;code = 65
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = m;code = 109
char = b;code = 98
char = i;code = 105
char = n;code = 110
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 = a;code = 97
char = n;code = 110
char = n;code = 110
char = e;code = 101
char = x;code = 120
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = V;code = 86
char = ;code = 32
char = l;code = 108
char = a;code = 97
char = b;code = 98
char = e;code = 101
char = l;code = 108
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = p;code = 112
char = i;code = 105
char = d;code = 100
char = i;code = 105
char = u;code = 117
char = m;code = 109
char = ;code = 32
char = i;code = 105
char = o;code = 111
char = d;code = 100
char = i;code = 105
char = d;code = 100
char = e;code = 101
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 = 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 = e;code = 101
char = v;code = 118
char = e;code = 101
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = h;code = 104
char = i;code = 105
char = g;code = 103
char = h;code = 104
char = e;code = 101
char = r;code = 114
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 = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = L;code = 76
char = -;code = 45
char = P;code = 80
char = A;code = 65
char = M;code = 77
char = ;code = 32
char = (;code = 40
char = 4;code = 52
char = 2;code = 50
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 = 41
char = ;code = 32
char = d;code = 100
char = i;code = 105
char = d;code = 100
char = ;code = 32
char = n;code = 110
char = o;code = 111
char = t;code = 116
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 = ;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 = 32
char = u;code = 117
char = n;code = 110
char = t;code = 116
char = i;code = 105
char = l;code = 108
char = ;code = 32
char = 4;code = 52
char = 8;code = 56
char = ;code = 32
char = h;code = 104
char = r;code = 114
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 = t;code = 116
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = t;code = 116
char = m;code = 109
char = e;code = 101
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char = t;code = 116
char = ,;code = 44
char = ;code = 32
char = b;code = 98
char = u;code = 117
char = t;code = 116
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = d;code = 100
char = u;code = 117
char = c;code = 99
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 = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = ;code = 32
char = d;code = 100
char = e;code = 101
char = a;code = 97
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
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char = m;code = 109
char = a;code = 97
char = r;code = 114
char = k;code = 107
char = e;code = 101
char = d;code = 100
char = l;code = 108
char = y;code = 121
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char = a;code = 97
char = c;code = 99
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = e;code = 101
char = r;code = 114
char = a;code = 97
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char = e;code = 101
char = d;code = 100
char = ;code = 32
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = a;code = 97
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char = r;code = 114
char = e;code = 101
char = s;code = 115
char = u;code = 117
char = l;code = 108
char = t;code = 116
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = G;code = 71
char = S;code = 83
char = H;code = 72
char = ;code = 32
char = d;code = 100
char = e;code = 101
char = p;code = 112
char = l;code = 108
char = e;code = 101
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = :;code = 58
char = ;code = 32
char = 4;code = 52
char = 8;code = 56
char = ;code = 32
char = h;code = 104
char = o;code = 111
char = u;code = 117
char = r;code = 114
char = s;code = 115
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 = L;code = 76
char = -;code = 45
char = P;code = 80
char = A;code = 65
char = M;code = 77
char = ;code = 32
char = (;code = 40
char = 4;code = 52
char = 2;code = 50
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 = 41
char = ;code = 32
char = t;code = 116
char = r;code = 114
char = e;code = 101
char = a;code = 97
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char = m;code = 109
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ,;code = 44
char = ;code = 32
char = G;code = 71
char = S;code = 83
char = H;code = 72
char = -;code = 45
char = d;code = 100
char = e;code = 101
char = p;code = 112
char = l;code = 108
char = e;code = 101
char = t;code = 116
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 = s;code = 115
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char = s;code = 115
char = h;code = 104
char = o;code = 111
char = w;code = 119
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = 4;code = 52
char = -;code = 45
char = f;code = 102
char = o;code = 111
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char = d;code = 100
char = ;code = 32
char = i;code = 105
char = n;code = 110
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char = r;code = 114
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = e;code = 101
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char = i;code = 105
char = n;code = 110
char = ;code = 32
char = D;code = 68
char = N;code = 78
char = A;code = 65
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char = f;code = 102
char = r;code = 114
char = a;code = 97
char = g;code = 103
char = m;code = 109
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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 = ;code = 32
char = a;code = 97
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char = ;code = 32
char = a;code = 97
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char = 7;code = 55
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char = f;code = 102
char = o;code = 111
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char = c;code = 99
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char = e;code = 101
char = a;code = 97
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char = e;code = 101
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char = i;code = 105
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
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char = f;code = 102
char = r;code = 114
char = a;code = 97
char = c;code = 99
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 = a;code = 97
char = p;code = 112
char = o;code = 111
char = p;code = 112
char = t;code = 116
char = o;code = 111
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char = i;code = 105
char = c;code = 99
char = ;code = 32
char = (;code = 40
char = a;code = 97
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char = n;code = 110
char = e;code = 101
char = x;code = 120
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = V;code = 86
char = -;code = 45
char = p;code = 112
char = o;code = 111
char = s;code = 115
char = i;code = 105
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = );code = 41
char = ;code = 32
char = c;code = 99
char = e;code = 101
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char = l;code = 108
char = s;code = 115
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char = a;code = 97
char = s;code = 115
char = ;code = 32
char = c;code = 99
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char = m;code = 109
char = p;code = 112
char = a;code = 97
char = r;code = 114
char = e;code = 101
char = d;code = 100
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char = t;code = 116
char = o;code = 111
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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 = n;code = 110
char = o;code = 111
char = r;code = 114
char = m;code = 109
char = a;code = 97
char = l;code = 108
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char = G;code = 71
char = S;code = 83
char = H;code = 72
char = ;code = 32
char = l;code = 108
char = e;code = 101
char = v;code = 118
char = e;code = 101
char = l;code = 108
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = V;code = 86
char = a;code = 97
char = r;code = 114
char = i;code = 105
char = o;code = 111
char = u;code = 117
char = s;code = 115
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char = e;code = 101
char = a;code = 97
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char = i;code = 105
char = t;code = 116
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char = e;code = 101
char = s;code = 115
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char = d;code = 100
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char = e;code = 101
char = v;code = 118
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char = t;code = 116
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char = t;code = 116
char = h;code = 104
char = i;code = 105
char = s;code = 115
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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 = a;code = 97
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char = n;code = 110
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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
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char = o;code = 111
char = f;code = 102
char = ;code = 32
char = G;code = 71
char = S;code = 83
char = H;code = 72
char = ;code = 32
char = d;code = 100
char = e;code = 101
char = p;code = 112
char = l;code = 108
char = e;code = 101
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = n;code = 110
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char = L;code = 76
char = -;code = 45
char = P;code = 80
char = A;code = 65
char = M;code = 77
char = ;code = 32
char = c;code = 99
char = y;code = 121
char = t;code = 116
char = o;code = 111
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char = o;code = 111
char = x;code = 120
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char = c;code = 99
char = i;code = 105
char = t;code = 116
char = y;code = 121
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char = ;code = 32
char = s;code = 115
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char = g;code = 103
char = g;code = 103
char = e;code = 101
char = s;code = 115
char = t;code = 116
char = i;code = 105
char = n;code = 110
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char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
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char = r;code = 114
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char = a;code = 97
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char = v;code = 118
char = e;code = 101
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char = x;code = 120
char = y;code = 121
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char = e;code = 101
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char = e;code = 101
char = c;code = 99
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char = e;code = 101
char = s;code = 115
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char = d;code = 100
char = o;code = 111
char = ;code = 32
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char = ;code = 32
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char = l;code = 108
char = a;code = 97
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char = ;code = 32
char = a;code = 97
char = ;code = 32
char = r;code = 114
char = o;code = 111
char = l;code = 108
char = e;code = 101
char = .;code = 46
char = ;code = 32
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 = d;code = 100
char = a;code = 97
char = t;code = 116
char = a;code = 97
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char = s;code = 115
char = h;code = 104
char = o;code = 111
char = w;code = 119
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char = t;code = 116
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char = a;code = 97
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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 = B;code = 66
char = S;code = 83
char = O;code = 79
char = ;code = 32
char = t;code = 116
char = r;code = 114
char = e;code = 101
char = a;code = 97
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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 = t;code = 116
char = h;code = 104
char = e;code = 101
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char = m;code = 109
char = o;code = 111
char = d;code = 100
char = e;code = 101
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char = o;code = 111
char = f;code = 102
char = ;code = 32
char = L;code = 76
char = -;code = 45
char = P;code = 80
char = A;code = 65
char = M;code = 77
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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 = c;code = 99
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result sql = Intracellular levels of glutathione have been shown to affect the sensitivity of cells to cell death-inducing stimuli, as well as the mode of cell death. We found in five human colorectal cancer cell lines (HT-29, LS-180, LOVO, SW837, and SW1116) that GSH depletion by L-buthionine-[S,R]-sulfoximine (BSO) below 20% of control values increased L-phenylalanine mustard (L-PAM; Melphalan) cytotoxicity 2- to 3-fold. Effects on kinetics of both cell cycle progression and cell death were further investigated in the HT-29 cell line. BSO treatment alone had no effect on cell cycle kinetics, but did enhance the inhibition of S phase progression as induced by L-PAM; at high concentration of of L-PAM, BSO pretreatment resulted in blockage in all phases of the cell cycle. Yet, BSO pretreatment did not affect the intracellular L-PAM content L-PAM : induced apoptosis in both normal and GSH-depleted cells. A combination of annexin V labeling and propidium iodide staining revealed that even the higher concentration of L-PAM (420 microM) did not induce apoptosis until 48 hr after treatment, but that induction of cell death was markedly accelerated as a result of GSH depletion: 48 hours after L-PAM (420 microM) treatment, GSH-depleted cells showed a 4-fold increase in DNA fragmentation and a 7-fold increase in the fraction of apoptotic (annexin V-positive) cells as compared to cells with normal GSH levels. Various antioxidant treatment modalities could not prevent this potentiating effect of GSH depletion on L-PAM cytotoxicity, suggesting that reactive oxygen species do not play a role. These data show that after BSO treatment the mode of L-PAM-induced cell death does not necessarily switch from apoptosis to necrosis.

Publication: Biochem. Pharmacol. 1999 Aug 15 ;58(4)::655-64.
Publication Date: 1999 Aug 15
Study Author(s): Vahrmeijer, A L;van Dierendonck, J H;Schutrups, J;van de Velde, C J;Mulder, G J;
Institution: Department of Surgery, Leiden University Medical Center, The Netherlands.
Shortcut link to this study:
Intracellular levels of glutathione have been shown to affect the sensitivity of cells to cell death-inducing stimuli, as well as the mode of cell death. We found in five human colorectal cancer cell lines (HT-29, LS-180, LOVO, SW837, and SW1116) that GSH depletion by L-buthionine-[S,R]-sulfoximine (BSO) below 20% of control values increased L-phenylalanine mustard (L-PAM; Melphalan) cytotoxicity 2- to 3-fold. Effects on kinetics of both cell cycle progression and cell death were further investigated in the HT-29 cell line. BSO treatment alone had no effect on cell cycle kinetics, but did enhance the inhibition of S phase progression as induced by L-PAM; at high concentration of of L-PAM, BSO pretreatment resulted in blockage in all phases of the cell cycle. Yet, BSO pretreatment did not affect the intracellular L-PAM content L-PAM : induced apoptosis in both normal and GSH-depleted cells. A combination of annexin V labeling and propidium iodide staining revealed that even the higher concentration of L-PAM (420 microM) did not induce apoptosis until 48 hr after treatment, but that induction of cell death was markedly accelerated as a result of GSH depletion: 48 hours after L-PAM (420 microM) treatment, GSH-depleted cells showed a 4-fold increase in DNA fragmentation and a 7-fold increase in the fraction of apoptotic (annexin V-positive) cells as compared to cells with normal GSH levels. Various antioxidant treatment modalities could not prevent this potentiating effect of GSH depletion on L-PAM cytotoxicity, suggesting that reactive oxygen species do not play a role. These data show that after BSO treatment the mode of L-PAM-induced cell death does not necessarily switch from apoptosis to necrosis.
PMID: 10413303

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