Interaction analyses of binary mixtures of carcinogenic PAHs using morphological cell transformation of C3H10T1/2CL8 mouse embryo fibroblasts in culture

Studies of defined mixtures of carcinogenic polycyclic aromatic hydrocarbon s (PAH) have identified three major categories of interactions: antagonism; synergism; and additivity depending on the biological model, tissue, route of exposure, and specific PAH. To understand the bases of these interactio ns we studied binary mixtures of benzo[a]pyrene (B[a]P) and dibenz[a,h]anth racene (DBA) in transformable C3H10T1/2C18 (C3H10T1/2) mouse embryo fibrobl ast cells in culture. C3H10T1/2 cells treated with binary mixtures of B[a]P and DBA gave less than additive morphological cell transformation based on response additivity. These results were consistent with those reported in mice and rats on the antagonistic effects of B[a]P and DBA on tumorigenesis . P-32-Postlabeling DNA adduct studies revealed that DBA reduced B [a]P-DNA adduct levels by 47% with no effect on DBA-DNA adduct levels. This suggest s that one mechanism for the inhibition of morphological cell transformatio n of binary mixtures of B[a]P and DBA is due to alterations in the metaboli c activation of B[a]P.