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char = m;code = 109
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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 = Methylated metabolites of arsenic trioxide are more potent than arsenic trioxide as apoptotic but not differentiation inducers in leukemia and lymphoma cells.

Methylated metabolites of arsenic trioxide are more potent than arsenic trioxide as apoptotic but not differentiation inducers in leukemia and lymphoma cells.

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char = o;code = 111
char = w;code = 119
char = t;code = 116
char = h;code = 104
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char = i;code = 105
char = n;code = 110
char = h;code = 104
char = i;code = 105
char = b;code = 98
char = i;code = 105
char = t;code = 116
char = i;code = 105
char = o;code = 111
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char = ;code = 32
char = a;code = 97
char = n;code = 110
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 = M;code = 77
char = e;code = 101
char = t;code = 116
char = h;code = 104
char = y;code = 121
char = l;code = 108
char = a;code = 97
char = r;code = 114
char = s;code = 115
char = i;code = 105
char = n;code = 110
char = e;code = 101
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char = o;code = 111
char = x;code = 120
char = i;code = 105
char = d;code = 100
char = e;code = 101
char = ;code = 32
char = (;code = 40
char = M;code = 77
char = A;code = 65
char = s;code = 115
char = (;code = 40
char = I;code = 73
char = I;code = 73
char = I;code = 73
char = );code = 41
char = O;code = 79
char = );code = 41
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = l;code = 108
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = e;code = 101
char = x;code = 120
char = t;code = 116
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = i;code = 105
char = o;code = 111
char = d;code = 100
char = o;code = 111
char = d;code = 100
char = i;code = 105
char = m;code = 109
char = e;code = 101
char = t;code = 116
char = h;code = 104
char = y;code = 121
char = l;code = 108
char = a;code = 97
char = r;code = 114
char = s;code = 115
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = ;code = 32
char = w;code = 119
char = e;code = 101
char = r;code = 114
char = e;code = 101
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char = m;code = 109
char = o;code = 111
char = r;code = 114
char = e;code = 101
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char = p;code = 112
char = o;code = 111
char = t;code = 116
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = g;code = 103
char = r;code = 114
char = o;code = 111
char = w;code = 119
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = h;code = 104
char = i;code = 105
char = b;code = 98
char = i;code = 105
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = s;code = 115
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char = a;code = 97
char = n;code = 110
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 = t;code = 116
char = i;code = 105
char = c;code = 99
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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 = r;code = 114
char = s;code = 115
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = i;code = 105
char = A;code = 65
char = s;code = 115
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char = I;code = 73
char = I;code = 73
char = I;code = 73
char = );code = 41
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = N;code = 78
char = B;code = 66
char = 4;code = 52
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 = 44
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = A;code = 65
char = P;code = 80
char = L;code = 76
char = ;code = 32
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = ;code = 32
char = l;code = 108
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = .;code = 46
char = ;code = 32
char = T;code = 84
char = h;code = 104
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 = a;code = 97
char = l;code = 108
char = s;code = 115
char = o;code = 111
char = ;code = 32
char = o;code = 111
char = b;code = 98
char = s;code = 115
char = e;code = 101
char = r;code = 114
char = v;code = 118
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = K;code = 75
char = 5;code = 53
char = 6;code = 54
char = 2;code = 50
char = ;code = 32
char = h;code = 104
char = u;code = 117
char = m;code = 109
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = l;code = 108
char = e;code = 101
char = u;code = 117
char = k;code = 107
char = e;code = 101
char = m;code = 109
char = i;code = 105
char = a;code = 97
char = ,;code = 44
char = ;code = 32
char = l;code = 108
char = y;code = 121
char = m;code = 109
char = p;code = 112
char = h;code = 104
char = o;code = 111
char = m;code = 109
char = a;code = 97
char = ;code = 32
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = ;code = 32
char = l;code = 108
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = s;code = 115
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = i;code = 105
char = m;code = 109
char = a;code = 97
char = r;code = 114
char = y;code = 121
char = ;code = 32
char = c;code = 99
char = u;code = 117
char = l;code = 108
char = t;code = 116
char = u;code = 117
char = r;code = 114
char = e;code = 101
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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
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char = i;code = 105
char = c;code = 99
char = ;code = 32
char = l;code = 108
char = y;code = 121
char = m;code = 109
char = p;code = 112
char = h;code = 104
char = o;code = 111
char = c;code = 99
char = y;code = 121
char = t;code = 116
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = l;code = 108
char = e;code = 101
char = u;code = 117
char = k;code = 107
char = e;code = 101
char = m;code = 109
char = i;code = 105
char = a;code = 97
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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 = 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 = h;code = 104
char = u;code = 117
char = m;code = 109
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = b;code = 98
char = o;code = 111
char = n;code = 110
char = e;code = 101
char = ;code = 32
char = m;code = 109
char = a;code = 97
char = r;code = 114
char = r;code = 114
char = o;code = 111
char = w;code = 119
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = g;code = 103
char = e;code = 101
char = n;code = 110
char = i;code = 105
char = t;code = 116
char = o;code = 111
char = r;code = 114
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 = 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 = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = s;code = 115
char = s;code = 115
char = o;code = 111
char = c;code = 99
char = i;code = 105
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = g;code = 103
char = r;code = 114
char = e;code = 101
char = a;code = 97
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char = e;code = 101
char = r;code = 114
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char = h;code = 104
char = y;code = 121
char = d;code = 100
char = r;code = 114
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char = e;code = 101
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char = d;code = 100
char = e;code = 101
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = c;code = 99
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char = m;code = 109
char = u;code = 117
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
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char = ;code = 32
char = a;code = 97
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char = d;code = 100
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char = i;code = 105
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char = i;code = 105
char = b;code = 98
char = i;code = 105
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 = g;code = 103
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char = u;code = 117
char = t;code = 116
char = a;code = 97
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char = h;code = 104
char = i;code = 105
char = o;code = 111
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char = e;code = 101
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char = e;code = 101
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char = i;code = 105
char = d;code = 100
char = a;code = 97
char = s;code = 115
char = e;code = 101
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char = a;code = 97
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char = t;code = 116
char = i;code = 105
char = v;code = 118
char = i;code = 105
char = t;code = 116
char = y;code = 121
char = .;code = 46
char = ;code = 32
char = M;code = 77
char = A;code = 65
char = s;code = 115
char = (;code = 40
char = I;code = 73
char = I;code = 73
char = I;code = 73
char = );code = 41
char = O;code = 79
char = ,;code = 44
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char = i;code = 105
char = n;code = 110
char = ;code = 32
char = c;code = 99
char = o;code = 111
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char = t;code = 116
char = r;code = 114
char = a;code = 97
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char = t;code = 116
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = i;code = 105
char = A;code = 65
char = s;code = 115
char = (;code = 40
char = I;code = 73
char = I;code = 73
char = I;code = 73
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char = ,;code = 44
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char = d;code = 100
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char = d;code = 100
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char = i;code = 105
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char = d;code = 100
char = u;code = 117
char = c;code = 99
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char = P;code = 80
char = M;code = 77
char = L;code = 76
char = -;code = 45
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char = i;code = 105
char = c;code = 99
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char = e;code = 101
char = c;code = 99
char = e;code = 101
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char = o;code = 111
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char = a;code = 97
char = l;code = 108
char = p;code = 112
char = h;code = 104
char = a;code = 97
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char = d;code = 100
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char = r;code = 114
char = a;code = 97
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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 = 44
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char = o;code = 111
char = r;code = 114
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char = r;code = 114
char = e;code = 101
char = s;code = 115
char = t;code = 116
char = o;code = 111
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char = e;code = 101
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char = P;code = 80
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char = L;code = 76
char = ;code = 32
char = n;code = 110
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char = c;code = 99
char = l;code = 108
char = e;code = 101
char = a;code = 97
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char = b;code = 98
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char = i;code = 105
char = e;code = 101
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char = d;code = 100
char = i;code = 105
char = f;code = 102
char = f;code = 102
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char = i;code = 105
char = o;code = 111
char = n;code = 110
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char = i;code = 105
char = n;code = 110
char = ;code = 32
char = N;code = 78
char = B;code = 66
char = 4;code = 52
char = ;code = 32
char = c;code = 99
char = e;code = 101
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char = s;code = 115
char = .;code = 46
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char = I;code = 73
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char = ;code = 32
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char = c;code = 99
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char = c;code = 99
char = u;code = 117
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char = i;code = 105
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char = i;code = 105
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char = H;code = 72
char = e;code = 101
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char = G;code = 71
char = 2;code = 50
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char = t;code = 116
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char = ;code = 32
char = N;code = 78
char = B;code = 66
char = 4;code = 52
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char = c;code = 99
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char = I;code = 73
char = I;code = 73
char = I;code = 73
char = );code = 41
char = .;code = 46
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char = H;code = 72
char = e;code = 101
char = p;code = 112
char = G;code = 71
char = 2;code = 50
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char = c;code = 99
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char = p;code = 112
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char = f;code = 102
char = e;code = 101
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char = i;code = 105
char = a;code = 97
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char = a;code = 97
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char = e;code = 101
char = d;code = 100
char = ;code = 32
char = b;code = 98
char = y;code = 121
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char = N;code = 78
char = B;code = 66
char = 4;code = 52
char = ;code = 32
char = c;code = 99
char = e;code = 101
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char = s;code = 115
char = .;code = 46
char = ;code = 32
char = T;code = 84
char = h;code = 104
char = i;code = 105
char = s;code = 115
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char = e;code = 101
char = x;code = 120
char = p;code = 112
char = e;code = 101
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char = n;code = 110
char = t;code = 116
char = a;code = 97
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char = o;code = 111
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char = g;code = 103
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char = a;code = 97
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char = v;code = 118
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char = v;code = 118
char = o;code = 111
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char = h;code = 104
char = e;code = 101
char = p;code = 112
char = a;code = 97
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char = ;code = 32
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char = ;code = 32
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char = ;code = 32
char = M;code = 77
char = A;code = 65
char = s;code = 115
char = (;code = 40
char = I;code = 73
char = I;code = 73
char = I;code = 73
char = );code = 41
char = O;code = 79
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char = ;code = 32
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char = p;code = 112
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char = s;code = 115
char = i;code = 105
char = d;code = 100
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char = r;code = 114
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char = d;code = 100
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
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
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = o;code = 111
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char = c;code = 99
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result sql = Treatment with arsenic trioxide (As(2)O(3)) by inducing apoptosis and partial differentiation of acute promyelocytic leukemia (APL) cells results in clinical remission in APL patients resistant to chemotherapy and all-trans-retinoic acid. As(2)O(3) (iAs(III)) is methylated in the liver to mono- and dimethylated metabolites, including methylarsonic acid, methylarsonous acid, dimethylarsinic acid, and dimethylarsinous acid. Methylated trivalent metabolites that are potent cytotoxins, genotoxins, and enzyme inhibitors may contribute to the in vivo therapeutic effect of iAs(III). Therefore, we compared the potency of iAs(III) and trivalent metabolites using chemical precursors of methylarsonous acid and dimethylarsinous acid to induce differentiation, growth inhibition, and apoptosis. Methylarsine oxide (MAs(III)O) and to a lesser extent iododimethylarsine were more potent growth inhibitors and apoptotic inducers than iAs(III) in NB4 cells, an APL cell line. This was also observed in K562 human leukemia, lymphoma cell lines, and in primary culture of chronic lymphocytic leukemia cells, but not human bone marrow progenitor cells. Apoptosis was associated with greater hydrogen peroxide accumulation and inhibition of glutathione peroxidase activity. MAs(III)O, in contrast to iAs(III), did not induce PML-retinoic acid receptor alpha degradation, or restore PML nuclear bodies or differentiation in NB4 cells. In a cocultivation experiment, hepatoma-derived HepG2 cells, but not NB4 cells, methylate radiolabeled iAs(III). Methylated metabolites released from HepG2 cells are preferentially accumulated by NB4 cells. This experimental model suggests that in vivo hepatic methylation of iAs(III) may contribute to As(2)O(3)-induced apoptosis but not differentiation of APL cells. MAs(III)O as an apoptotic inducer should be considered in the treatment of other hematologic malignancies like lymphoma.

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