AFLATOXIN B-1 8,9-EPOXIDE HYDROLYSIS IN THE PRESENCE OF RAT AND HUMANEPOXIDE HYDROLASE

Aflatoxin B-1 (AFB(1)) must be activated to the electrophilic AFB(1) e xo-8,9-epoxide to be genotoxic and carcinogenic. A role for epoxide hy drolase in detoxication has been suggested but never directly addresse d. In light of recent studies determining the instability of AFB(1) ex o-8,9-epoxide in H2O, a role for epoxide hydrolase appears dubious. Ra t liver or recombinant rat epoxide hydrolase provided an enhancement t o the already fast hydrolysis rate of up to 22%. Purified human epoxid e hydrolase provided no detectable enhancement to the rate of chemical hydrolysis. Some reduction in the genotoxicity of AFB(1) was observed when the ratio of rat epoxide hydrolase to cytochrome P450 was high ( similar to 50-fold). An 80-fold excess of human epoxide hydrolase over cytochrome P450 only produced an effect of similar to 25% inhibition. It appears, therefore, that there is little evidence to support a rol e for epoxide hydrolase in the detoxicatian of AFB(1).