Protection of cultured hamster embryonic cells from 7,12-dimethylbenz(a)anthracene cytotoxicity and the induced synthesis of aryl hydroxylase.

Treatment of secondary cultures of hamster embryonic cells with an excess of thymidine (5mM) caused an inhibition of DNA synthesis which was reversible. This treatment permitted a study of the effects of polycyclic hydrocarbons on cells inhibited at the G1-S boundary and on cells entering the S phase of the cell cycle. Cytotoxic damage caused by 7,12dimethylbenz(a)anthracene (DMBA) treatment of cells after their release from thymidine inhibition was prevented by the simultaneous exposure to an equimolar concentration of benz(a)anthracene (BA) (4~M). The DMBA depression of the rate of DNA synthesis and the inhibition of cell division were also prevented by simultaneous BA treatment. These results suggest that protection from DMBA cytotoxicity may be due to a BA induction of aryl hydroxylase which may have degraded the DMBA to less toxic metabolites. DNA synthesis was shown not to be required for induction of aryl hydroxylase; in fact, an equal amount of the enzyme activity was induced during either synthesis or inhibition of DNA. Cultures induced simultaneously with BA + DMBA synthesized a higher level of aryl hydroxylase than cultures with either BA or DMBA.