The covalent interaction of the diastereomers of benzo[a]-pyrene-7, 8-diol-9, 10-epoxide (BPDE) with macromolecules of mouse epidermis was investigated following topical application in vivo. Levels of carcinogen bound to DNA, RNA and protein after various exposure times were determined for the whole epidermis, as well as for the purified basal cell population. In mice exposed for 3 h to either diastereomer, 3 times more racemic (±)BPDE-syn than racemic (±)BPDE-anti was bound to DNA isolated from whole epidermis. A similar pattern was observed in the relative levels of BPDE-syn and -anti detected in whole epidermal RNA and protein. After 12 h of exposure in vivo, no significant difference was detected in the amounts of BPDE-anti and syn covalently bound to each class of macromolecule purified from whole epidermis. Following 24 h of exposure in vivo - 2 times more BPDE-anti than -syn was detected in DNA from whole epidermis. Binding of BPDE-anti was also demonstrated to be higher than BPDE-syn in whole epidermal RNA and protein at this time point. These results would suggest that the diastereomers exhibited two different time courses of covalent binding in whole epidermis. When binding of the anti and syn diastereomers of BPDE was compared in the basal cell population following various exposure times in vivo, nearly equivalent levels of both diastereomers were detected in the DNA, RNA and protein at all three time points. Since the epidermal basal cell layer is the presumed target cell population for initiation, the absence of any observable difference between the amount of anti-diastereomer (the carcinogenic form) and syn-diastereomer (the non-carcinogenic form) bound to basal DNA would suggest a lack of correlation between extent of DNA binding and the previously reported carcinogenicity of the diastereomers.
ASJC Scopus subject areas
- Cancer Research