| [Background] Inorganic arsenic is a definite human carcinogen that occurs ubiquitously in natural environment and tow-dose exposure to it for a long term can cause significant increase in risk for human cancers of the skin, lung, liver, kidney, bladder and prostate. However, unlike most carcinogens, arsenic compound is not a specific mutagenic agent and unable to induce gene mutation and DNA damage, such as break and crosslink of DNA strand and formation of DNA adducts. But, arsenic can induce morphological transformation, chromosomal aberrations, increased sister chromatid exchanges and micronuclei in the cultured cells. So far, the experimental animal model with cancer caused by arsenic has not been established yet and molecular mechanism of carcinogenesis by arsenic was poorly understood. Recently, the attempts to study arsenic-induced caicinogenic mechanism has been made with both molecular biological methods and metabolic methylation pathways of arsenic.The inorganic arsenic can become organic arsenic with biological transformation of methyl group in vivo by a methyltransferase(MTase), using S-adenosylmethione (SAM) as a donor for methyl group. In usual condition, DNA MTase also requires SAM as a donor for methyl group in modification of DNA methylation -demethylation in eukaryotes. Therefore, it is proposed that arsenic - induced caicinogenecity be caused as a result of interference with normal pathway of DNA methylation in the bodies, affecting DNA damage and repair, modulation of cell cycle and cell differentiation. Alteration in DNA methylation can cause gene mutation and its abnormal expression. A lot of studies in ths past few years showed that perturbation of DNA methylation is common in the neoplasm tissues, especially hypermethylation of CpG islands of the promoter region in tumor suppressor gene, which silences the genes and can be observed at early stage of oncogenesis, thus giving rise to a novel pathway to cause their progressive epigenetic inactivation.
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