Hepatocarcinogenic potency of mixed and pure enantiomers of trans-7,8-dihydrobenzo[a]pyrene-7,8-diol in trout.
The hepatocarcinogenic potency of pure and racemic trans-7,8-dihydrobenzo[a]pyrene-7,8-diol was investigated in embryos and sac-fry rainbow trout. Embryos microinjected with (+/-)-trans-7,8-dihydrobenzo[a]pyrene-7,8-diol ((+/-) BP-7,8-DHD) developed liver tumors 9 months after hatching. However, this exposure protocol resulted in high mortalities. Microinjection of newly hatched sac-fry with 0.01-1.0 microgram of (+/-) BP-7,8-DHD resulted in a dose-dependent production of liver tumors (0-13%) similar to the results with embryos but without the problem of high mortalities. Co-injection of sac-fry with (+/-) BP-7,8-DHD and either beta-naphthoflavone or carbon tetrachloride significantly enhanced the tumor response (approx. 3-fold). The relative carcinogenic potencies of the pure (+) and (-) enantiomers of BP-7,8-DHD were evaluated by microinjection into sac-fry at doses of 0.5-5.0 micrograms. The results demonstrated that the (-) enantiomer was 4-18 times more potent than the (+). Mixed carcinomas were the most prevalent liver tumors observed. These results demonstrate that trout embryos and sac-fry are both responsive to hepatocarcinogenesis initiation by injection with BP-7,8-DHD. The marked enhancement seen with co-injection of sac-fry with beta-naphthoflavone or carbon tetrachloride suggests that both cytochrome P-450-dependent and lipid peroxidation-dependent pathways could be involved in bioactivation of this compound, presumably through epoxidation at the 9,10-position. As is the case with mammals, the (-) enantiomer of BP-7,8-DHD is a more potent carcinogen than the (+) enantiomer.
Kelly
J D
JD
Toxicology Program, Oregon State University, Corvallis 97331-6602.
Dutchuk
M
M
Hendricks
J D
JD
Williams
D E
DE
D000818:Animals; D001571:Benzoflavones / Q000494:pharmacology; D002251:Carbon Tetrachloride / Q000494:pharmacology; D004101:Dihydroxydihydrobenzopyrenes / Q000633:toxicity*; D004195:Disease Models, Animal; D004625:Embryo, Nonmammalian; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced*; D008845:Microinjections; D013237:Stereoisomerism; D014337:Trout; D019324:beta-Naphthoflavone
D001571:Benzoflavones; D004101:Dihydroxydihydrobenzopyrenes; D019324:beta-Naphthoflavone; D002251:Carbon Tetrachloride