Epigenetic Regulation in Environmental Chemical Carcinogenesis and its Applicability in Human Health Risk Assessment

The objective of this study is to investigate the relationship between the points of departure (PODs) for cancer incidence and DNA methylation changes in laboratory animals exposed to the following environmental toxicants: bromodichloromethane, dibromochloromethane, chloroform, hydrazine, trichloroethylene, benzidine, trichloroacetic acid, and di(2-ethylhexyl) phthalate (DEHP; a known reproductive toxicant). The results demonstrate that the PODs for cancer incidence and altered DNA methylation are similar. Furthermore, based on the available data, the POD for DNA methylation appeared more sensitive compared to that for cancer incidence following the administration of DEHP to rats during different life stages. The high degree of correlation between PODs for cancer incidence and DNA methylation (for both total DNA and individual genes) suggests that DNA methylation end points could potentially be used as a screening tool in predicting the potential toxicity/carcinogenicity and in prioritizing large numbers of chemicals with sparse toxicity databases. The life stage during which treatment occurs is also an important consideration when assessing the potential application of epigenetic end points as a screening tool.

Source: International Journal of Toxicology - September 13, 2015 Category: Toxicology Authors: Kuppusamy, S. P., Kaiser, J. P., Wesselkamper, S. C. Tags: Regular Articles Source Type: research