SYNERGISTIC EFFECTS OF CHLORDANE AND TPA IN MULTISTAGE MORPHOLOGICAL TRANSFORMATION OF SHE CELLS

The cyclodiene pesticide chlordane has been reported to be a non-genotoxic carcinogen in rodents. The effects of chlordane on SHE cell transformation were investigated in this study. It appeared that chlordane exhibited a weak transforming activity when applied repeatedly at 8 mu g/ml. No effect resulted from the combination of benzo[a]pyrene-chlordane. In contrast, chlordane in the range 5-20 mu g/ml and 12-O-tetradecanoylphorbol-13-acetate (TPA) (0.1 mu g/ml) highly potentiated each other when applied sequentially. The synergistic effects could be inhibited by dexamethasone. These results led us to study the genotoxicity of chlordane on SHE cells: no DNA adduct formation could be detected in SHE cells treated with chlordane at a concentration potentiating the transforming effect of TPA. We also confirmed that this pesticide markedly inhibited intercellular communication between SHE as well as V79 cells. These results support literature data on the non-genotoxicity of chlordane. Overall, this study highlights the fact that interaction between-non genotoxic carcinogens may enhance the transformation frequency of SHE cells. Thus, combined effects must be taken into account in the evaluation of carcinogenic risk.