Inactivation of p15INK4b in chronic arsenic poisoning cases
| Autor: | Xue Han, Xiao-Wen Zeng, Lifang Wang, Aihua Zhang, Daochuan Li, Chen Gao, Wen Chen, Liping Chen, Chun Yu |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Health
Toxicology and Mutagenesis Physiology chemistry.chemical_element Human skin p15INK4b Biology Toxicology medicine.disease_cause Arsenic Lesion lcsh:RA1190-1270 medicine Homozygous deletion Carcinogen lcsh:Toxicology. Poisons Genetics DNA methylation integumentary system Skin lesions Cancer medicine.disease Domestic coal use chemistry Skin cancer medicine.symptom Carcinogenesis |
| Zdroj: | Toxicology Reports, Vol 1, Iss C, Pp 692-698 (2014) |
| ISSN: | 2214-7500 |
| DOI: | 10.1016/j.toxrep.2014.08.007 |
| Popis: | 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 μg/L, 5.16 vs 1.36 μg/g). Subjects with higher arsenic concentrations are more likely to have p15INK4b methylation and gene deletion (χ2 = 4.28, P = 0.04 and χ2 = 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 (χ2 = 12.82, P < 0.01 and χ2 = 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. |
| Databáze: | OpenAIRE |
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