Correlation of Carcinogenic Potency with Mouse-Skin (32)P-Postlabeling and Muta-(R)Mouse lac Z(-)Mutation Data for DMBA and Its K-Region Sulphur Isostere: Comparison with Activities Observed in Standard Genotoxicity Assays

摘要

The genotoxicities in vitro and in vivo of the mouse-skin carcinogen 7,12-dimethylbenz(a)anthracene (DMBA) have been compared with those of its weakly carcinogenic 4,5-sulphur analogue, 6,11-dimethylbenzo(b)naphtho-(2,3-d)thiophene (S-DMBA). The only datasets that correlated with the relative carcinogenicity of these agents to the skin were those conducted using topically exposed mouse skin. Thus, both chemicals induced lacZ(-) mutations in the skin of lacZ(+) transgenic mice, and both produced DNA adducts on mouse-skin DNA as assessed using the (sup 32) P-postlabeling technique. The molecular geometry of DMBA and S-DMBA are compared, and divergent CASE predictions of activity in the Salmonella assay and skin-painting bioassay are discussed. (Copyright (c) 1993 Elsevier Science Publishers B.V.)