Mouse skin tumor promotion by sodium arsenate is associated with enhanced PCNA expression

Drinking water contamination by arsenicals remains a major public health problem in many parts of the world more particularly in India and Bangladesh. Despite arsenic being a health hazard and implicated in human carcinogenesis, the experimental evidence available is much limited even now and the mechanisms involved during carcinogenesis and tumor promotions are not clear. Accordingly, in this study, we have studied the tumor promoter effects of sodium arsenate on mouse skin tumor promoter model system using 9,10-dimethyl-1,2-benzanthracene (DMBA) as a initiating carcinogen. Our studies showed development of papillomas on mice skin treated with only DMBA. However, mice treated with DMBA on skin and administered arsenate (As) in drinking water showed development of well differentiated squamous cell carcinomas. Further, both by immunohistochemistry and western blotting analysis studies higher levels of proliferating cell nuclear antigen (PCNA) was observed in mice treated with DMBA plus arsenate compared to only DMBA treated group. PCNA is known to be associated with S phase and DNA replication of the cell cycle. The plain controls and arsenate controls did not show significant difference either in tumor development or in PCNA levels. The present study demonstrates mouse skin tumor promoting effect of arsenate which seems to be associated with abnormal cell proliferation as indicated by higher levels of PCNA expression. (c) 2004 Elsevier Ireland Ltd. All rights reserved.