Benzo(a)pyrene metabolism by rat liver microsomes: effects of adding purified glutathione S-transferases A, B, and C.
We have examined the effects of adding glutathione and isolated cytosolic glutathione S-transferases A, B, and C to rat liver microsomes metabolizing benzo(a)pyrene. Addition of glutathione alone resulted in the conjugation of 15 to 20% of the total metabolites of benzo(a)pyrene, and this conjugation could be inhibited almost entirely by bromosulfophthalein (an inhibitor of glutathione S-transferases), indicating that it is catalyzed by the glutathione S-transferase present in microsomes. Addition of purified cytosolic glutathione S-transferases A, B, and C yielded about 30 to 40% conjugate formation. Analysis of metabolites by high-pressure liquid chromatography demonstrated that the formation of 4,5-diol of benzo(a)pyrene was decreased by at least 80% by conjugation and that the 7,8-diol was also decreased significantly (40 to 60%). In addition, it was found that glutathione S-transferase B is capable of conjugating benzo(a)pyrene 1,6- and 3,6-quinones.
D000818:Animals; D001564:Benzo(a)pyrene; D001580:Benzopyrenes / Q000378:metabolism*; D002273:Carcinogens / Q000378:metabolism*; D003600:Cytosol / Q000201:enzymology; D005982:Glutathione Transferase / Q000302:isolation & purification / Q000378:metabolism*; D007700:Kinetics; D008099:Liver / Q000201:enzymology; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D001580:Benzopyrenes; D002273:Carcinogens; D001564:Benzo(a)pyrene; D005982:Glutathione Transferase