Correlation between DNA damage and GST-P in hepatocytes of juvenile rats treated with diethylnitrosamine

Abstract

DEN in drinking water. These two assays were performed in the three primary lobes ［ left （ L ） , right median （ RM ） and right anterior （ RA ）］ of the liver simultaneously which helped to clearly show the correlation between the two endpoints. Summary We investigated the relationship between DNA damage detected as single strand breaks using a Comet assay and the expression of glutathione S-transferase P-form （ GST-P ） as a marker of the early stage of carcinogenesis. In this study, 4-week-old rats were exposed to 10 or 40 ppm diethylnitrosamine （ DEN ） in drinking water for 14 days, then both DNA damage and GST-P expression were evaluated in the three primary lobes ［ left （ L ） , right median （ RM ） and right anterior （ RA ）］ of the liver to clarify the correlation between two endpoints within the organ over time. Both DNA damage and GST-P expression increased almost in parallel in a dose- and time-depen-dent manner in all lobes, and those had a good relationship with heterogeneous response, L ≧ RM>RA. Therefore, it was confirmed that the result of the Comet assay could correspond to the histopathological changes appearing in the initiation stage in rat hepatocytes.