The potential of carp to bioactivate benzo[a]pyrene to metabolites that bind to DNA.
We have investigated the formation of DNA adducts in starved, fed and 5,6-benzoflavone-pretreated carp following i.p. administration of benzo(a)pyrene. 32P-postlabeling analysis of the liver DNAs showed the presence of one predominant (greater than 92%) adduct in all three groups. Cochromatography experiments revealed that the main adduct was identical to authentic BPDEI-dG (10 beta-(deoxyguanosin-N2-yl)-7 beta, 8 alpha, 9 alpha-trihydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene). The formation of the adduct was evident as early as 1.5 h post-treatment and the levels increased steadily up to 7 days, reaching about 125, 110 and 102 attomole/microgram DNA in starved, fed and benzoflavone-pretreated carp, respectively. During this period, the benzo[a]pyrene-induced benzo[a]-pyrene monooxygenase activity increased from the uninduced, natural level of about 3 pmol/mg per min to levels of 35, 62 and 79 pmol/mg per min in starving, fed and 5,6-benzoflavone pretreated fish, respectively. A slow but steady formation of the diolepoxide-dG adduct was also observed in the liver DNA of carp following p.o. treatment. These results indicate that carp can biotransform polycyclic aromatic hydrocarbons such as benzo[a]pyrene to 'reactive' metabolites that bind to DNA.
Kurelec
B
B
Center for Marine Research Zagreb, Ruder Bosković Institute, Croatia, Yugoslavia.
Krca
S
S
Garg
A
A
Gupta
R C
RC
D000818:Animals; D001564:Benzo(a)pyrene / Q000378:metabolism*; D001571:Benzoflavones / Q000494:pharmacology; D001579:Benzopyrene Hydroxylase / Q000378:metabolism; D001711:Biotransformation; D002347:Carps / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D004249:DNA Damage; D008099:Liver / Q000378:metabolism; D019324:beta-Naphthoflavone
D001571:Benzoflavones; D001564:Benzo(a)pyrene; D019324:beta-Naphthoflavone; D004247:DNA; D001579:Benzopyrene Hydroxylase