چکیده (انگلیسی):

Arsenic exposure from burning high arsenic-containing coal has been associated with
human skin lesion and cancer. However, the mechanisms of arsenic-related carcinogenesis
are not fully understood. Inactivation of critical tumor suppression genes by epigenetic regulation
or genetic modification might contribute to arsenic-induced carcinogenicity. This
study aims to clarify the correlation between arsenic pollution and functional defect of
p15INK4b gene in arsenic exposure residents from a region of Guizhou Province, China. To
this end, 103 arsenic exposure residents and 105 control subjects were recruited in this
study. The results showed that the exposure group exhibited higher levels of urinary and
hair arsenic compared with the control group (55.28 vs 28.87 g/L, 5.16 vs 1.36 g/g). Subjects
with higher arsenic concentrations are more likely to have p15INK4b methylation and
gene deletion (2 = 4.28, P = 0.04 and 2 = 4.31, P = 0.04). We also found that the degree of
p15INK4b hypermethylation and gene deletion occurred at higher incidence in the poisoning
cases with skin cancer (3.7% and 14.81% in non-skin cancer group, 41.18% and 47.06 in skin
cancer group), and were significantly associated with the stage of skin lesions (2 = 12.82,
P < 0.01 and 2 = 7.835, P = 0.005). These observations indicate that inactivation of p15INK4b
through genetic alteration or epigenetic modification is a common event that is associated
with arsenic exposure and the development of arsenicosis.