Metabolism of benzo[a]pyrene and persistence of DNA adducts in the brown bullhead (Ictalurus nebulosus).
1. The in vitro metabolism of [3H]benzo[a]pyrene (BP) and [14C]benzo[a]pyrene-7,8-dihydrodiol (BP-7,8-diol) by liver of brown bullhead (Ictalurus nebulosus) was characterized, as was the formation and persistence of BP-DNA adducts in vivo. 2. Compared to rat liver microsomes, bullhead liver microsomes produced relatively larger amounts of BP-7,8-diol (predominantly the [-] enantiomer) and smaller amounts of of BP-7,8-diol (predominantly the [-] enantiomer) and smaller amounts of BP-4,5-diol. 3. BP phase I metabolites were efficiently converted by freshly isolated bullhead hepatocytes to conjugates, predominantly glucuronides. 4. BP-7,8-diol was metabolized by hepatocytes 4-fold more rapidly than was BP and was converted to approximately equal amounts of glucuronides, glutathione conjugates and sulfates. 5. BP-DNA adducts formed in bullhead liver with a lag time of several days and maximum adduct formation at 25-30 days. The major adduct was anti-BPDE-deoxyguanosine.
Division of Environmental Toxicology and Chemistry, State University of New York College Buffalo 14222.
H C
HC
Sikka
A R
AR
Steward
C
C
Kandaswami
J P
JP
Rutkowski
J
J
Zaleski
S
S
Kumar
K
K
Earley
R C
RC
Gupta
D000818:Animals; D001564:Benzo(a)pyrene / Q000378:metabolism*; D004247:DNA / Q000378:metabolism*; D005260:Female; D007059:Ictaluridae / Q000378:metabolism*; D008658:Inactivation, Metabolic / Q000502:physiology; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D051381:Rats; D014874:Water Pollutants, Chemical / Q000378:metabolism*
D014874:Water Pollutants, Chemical; D001564:Benzo(a)pyrene; D004247:DNA