This week's artwork was donated by Kate, a pediatric cancer patient who received treatment at The Children's Hospital of Philadelphia . Arsenite induces p53 accumulation through an ATM-dependent pathway in human fibroblasts. The molecular basis and clinical management of ataxia telangiectasia. Haplotypes at ATM identify coding-sequence variation and indicate a region of extensive linkage disequilibrium.
Arsenic compounds are potent human carcinogens.
Accumulated evidence has shown that arsenite-induced cytogenetic alterations are associated with the carcinogenicity of arsenic. Because p53 plays a guarding role in maintaining genome integrity and accuracy of chromosome segregation, the mechanistic effects of arsenite on p53 activation were analyzed. Accompanying the appearance of DNA strand breaks was a significant accumulation of p53 in arsenite-treated HFW cells, as demonstrated by immunoblotting and immunofluorescence techniques. For confirmation, we demonstrated that arsenite treatment, similar to X-ray irradiation, did not induce p53 accumulation in GM3395 fibroblasts derived from a patient with ataxia telangiectasia. In contrast, UV irradiation did cause p53 accumulation in these cells.