CORRELATION OF CARCINOGENIC POTENCY WITH MOUSE-SKIN P-32 POSTLABELINGAND MUTA-RMOUSE LAC Z- MUTATION DATA FOR DMBA AND ITS K-REGION SULFURISOSTERE - COMPARISON WITH ACTIVITIES OBSERVED IN STANDARD GENOTOXICITY ASSAYS

The genotoxicities in vitro and in vivo of the mouse-skin carcinogen 7 ,12-dimethylbenza!anthracene (DMBA) have been compared with those of its weakly carcinogenic 4,5-sulphur analogue, 6,11-dimethyl-benzob!na phtho-2,3-d!thiophene (S-DMBA). The only datasets that correlated wit h the relative carcinogenicity of these agents to the skin were those conducted using topically exposed mouse skin. Thus, both chemicals ind uced lacZ- mutations in the skin of lacZ+ transgenic mice, and both pr oduced DNA adducts on mouse-skin DNA as assessed using the P-32-postla beling technique. In each case, DMBA gave a stronger response than did S-DMBA. In contrast to these responses, only DMBA was active in the m ouse bone-marrow micronucleus assay and in the C3H10T1/2 in vitro cell transformation assay. Both chemicals were mutagenic to Salmonella and of approximately equal potency. The molecular geometry of DMBA and S- DMBA are compared, and divergent CASE predictions of activity in the S almonella assay and skin-painting bioassay are discussed. The importan ce of conducting predictive genotoxicity assays in systems close to th ose in which carcinogenicity is to be assessed is emphasized by these data.