Involvement of p53

Although As2O3 does not increase p53 or activity in most cells, a marked increase in p53 protein level was seen during As2O3-induced apoptosis in a human gastric cancer cell line, while co-incubation with the p53 anti-sense oligonucleotide suppressed both p53 overexpression and apoptosis induced by As2O3.64 In MBC-1, a B-cell lymphoma line, As2O3 exposure caused upregula-tion of p53 expression, resulting in caspase activation and, ultimately, apoptosis.65 p53 accumulation was also implicated in the mechanism by which As2O3 treatment induced apoptosis and G1-phase arrest in human T-cell lymphotropic virus type 1-infected cells.66

However, the role of p53 in arsenic-related cellular effects is still obscure. No difference in sensitivity to arsenic was found between fibroblast bearing p53

and fibroblast deficient in this gene, strongly suggesting that p53 is not involved.67 Hence, the relationship of p53 and arsenic in carcinogenesis or in cancer therapy could be cell- and tissue-type-specific and depends on dose and cellular environment.22

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