Inversion of enantioselectivity in glutathione conjugation of 9,10-dihydrobenzo[a]pyrene 7,8-oxide in hepatic cytosol of rats following induction of hepatic hyperplastic nodules by chemical carcinogens.
Enantiomers of 9,10-dihydrobenzo[a]pyrene 7,8-oxide (DBPO) were stereoselectivity conjugated with glutathione (GSH) specifically at benzylic carbon (C7) in normal Sprague--Dawley (SD) rat liver cytosol: (7R,8S)-(+)- greater than (7S,8R)-(-)-DBPOs. In contrast, in liver cytosol of SD rats bearing hepatic hyperplastic nodules induced with chemical carcinogens, (7S,8R)-(-)-DBPO was preferentially conjugated with GSH to (7R,8S)-(+)-DBPO. GSH S-transferases (GSTs) having sub-unit protein 4 were strongly suggested to play an important role in the preferential conjugation of (7R,8S)-(+)-DBPO in the normal rat liver cytosol, while the preferential conjugation of (7S,8R)-(-)-DBPO in the liver cytosol of the rat bearing hepatic hyperplastic nodules, was most likely to be attributable to GST 7-7, a characteristically induced protein in the hepatic hyperplastic nodules.
Department of Hygienic Chemistry, Tokyo College of Pharmacy, Japan.
A
A
Hiratsuka
K
K
Kawashima
T
T
Watabe
K
K
Satoh
I
I
Hatayama
K
K
Sato
D000818:Animals; D001580:Benzopyrenes / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism*; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008114:Liver Neoplasms, Experimental / Q000378:metabolism*; D008297:Male; D011230:Precancerous Conditions / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013237:Stereoisomerism
D001580:Benzopyrenes; C023387:9,10-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene; D005978:Glutathione