Mutagenicity and cytotoxicity of haloethanes as studied in the CHO/HGPRT system.

When haloethanes were being tested as direct-acting agents in the Chinese hamster ovary cell/hypoxanthine-guanine phosphoribosyl transferase (CHO/HGPRT) system, ethylene dibromide (EtBr2) exhibited more cytotoxic and mutagenic activity than ethylene dichloride (EtCl2), and the mixed halogenated congener ethylene bromochloride (EtBrCl) had an intermediate effect. On a molar basis, the relative mutagenic activity of EtBr2 : EtBrCl : EtCl2 was approximately 100 : 6 : 1. Cell survival was reduced to 50% by approx. 3, 6 and 50 mM of EtBr2, EtBrCl and EtCl2, respectively, and declined precipitously with increasing concentrations of the haloethanes. When these 3 haloethanes were assayed in the presence of S9, there was a 5-25-fold increase in cytotoxicity; however, only EtBrCl and EtCl2 also showed a concomitant increase in mutagenicity of 4-fold. The mutagenicity of EtBr2 remained unchanged when assayed in the presence of S9. When NADP was omitted from the S9 mix, which contains a NADPH-regenerating system, the increase in cytotoxicity and mutagenicity observed with the complete S9 mix was abolished. EtBr2 was shown to possess a molar equivalent mutagenic activity to ethyl methanesulfonate under the conditions of the assay. The cytotoxicity of EtBr2 increased as the time of treatment increased up to 24 h, while mutation induction appeared to peak at around 5 h.