Activation and deactivation of aflatoxin B1 in isolated rat hepatocytes.
Isolated rat hepatocytes took up [3H]-aflatoxin B1 during incubation with fifty percent of the aflatoxin B1 covalantly bound to cellular macromolecules. The amount of bound-aflatoxin B1 was proportional to the medium concentration of aflatoxin B1. The specific radioactivity (pmole/mg) of aflatoxin B1 found in the DNA fraction was 20 fold greater than that associated with protein. Metyrapone (0.75 mM) inhibited significantly the uptake and binding whereas 1,2-epoxy-3,3,3-trichloropropane (0.5 mM) enhanced 2-3 fold both the uptake and binding. Glutathione (0.25 mM) reduced these processes. Results indicate that a transformation of aflatoxin B1 is catalyzed by cytochrome P-450 mixed function oxidase and aflatoxin B1-2,3-epoxide so formed is primarily deactivated by epoxide hydrolase. In the isolated hepatocyte depletion of the epoxide by glutathione apparently has an insignificant role in aflatoxin detoxication.
D016604:Aflatoxin B1; D000348:Aflatoxins / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D001711:Biotransformation; D005978:Glutathione / Q000494:pharmacology; D066298:In Vitro Techniques; D008658:Inactivation, Metabolic; D008099:Liver / Q000378:metabolism*; D008797:Metyrapone / Q000494:pharmacology*; D006899:Mixed Function Oxygenases / Q000502:physiology; D051381:Rats; D014239:Trichloroepoxypropane / Q000494:pharmacology
D000348:Aflatoxins; D014239:Trichloroepoxypropane; D016604:Aflatoxin B1; D006899:Mixed Function Oxygenases; D005978:Glutathione; D008797:Metyrapone