Comparative effect of dietary butylated hydroxyanisole and beta-naphthoflavone on aflatoxin B1 metabolism, DNA adduct formation, and carcinogenesis in rainbow trout.
Butylated hydroxyanisole (BHA) and beta-naphthoflavone (BNF), both chemicals with anti-carcinogenic properties in some experimental animals, were compared for effects on aflatoxin B1 (AFB1) metabolism, hepatic DNA adduct formation and carcinogenesis in the rainbow trout. Dietary BHA had no effect on the hepatic tumor incidence when fed at 0.03 or 0.3% 4 weeks prior to and during a 4 week dietary exposure of 10 p.p.b. AFB1. BNF, when fed at 0.005 or 0.05% under similar conditions, significantly reduced tumor response, which confirms previous results in trout (Nixon et al., Carcinogenesis, 5, 615-619, 1984). BHA fed at either 0.03 or 0.3% for 8 weeks had no post-initiation effect on the 52 week hepatic tumor incidence of trout exposed to a 0.5 p.p.m. AFB1 solution as embryos. A similar post-initiation exposure to 0.05% BNF significantly enhanced AFB1 tumor response. The influence of dietary BHA and BNF on AFB1 metabolism and DNA adduct formation and persistence in trout were examined. A 3 week pre-treatment with 0.3% dietary BHA had no effect on in vivo hepatic nuclear AFB1-DNA adduct formation at 0.5, 1, 2 and 7 days after AFB1 i.p. injection. By contrast 0.05% dietary BNF reduced hepatic AFB1-DNA adducts to 33-60% of control levels at 0.5, 1, 2 and 4 days after AFB1 exposure. This was accompanied by significantly lower blood and liver levels of AFB1 during the first 24 h after i.p. injection. Livers of BNF trout also contained 4-fold more of the less carcinogenic metabolite, aflatoxin M1, and 50% less aflatoxicol (AFL), a metabolite with similar carcinogenicity as AFB1. Bile AFL-glucuronide levels were significantly decreased in BNF-fed trout, but total bile glucuronides were significantly increased due to a 15-fold increase in aflatoxicol-M1 glucuronide. Freshly isolated hepatocytes from BHA-fed fish, when incubated with AFB1 for 1 h, showed no difference in levels of AFB1-DNA adducts or ratios of AFB1 metabolites when compared to hepatocytes isolated from fish fed a control diet only. By contrast, dietary BNF has been previously shown to greatly enhance AFM1 production, reduce AFL production, and significantly reduce AFB1-DNA adduct formation in isolated trout hepatocytes (Bailey et al., Natl. Cancer Inst. Monograph, 65, 379-385, 1984). These results indicate that dietary BHA up to 0.3% does not alter AFB1 metabolism or DNA adduction in trout, nor does it inhibit or promote AFB1 hepatocarcinogenesis in this species.(ABSTRACT TRUNCATED AT 400 WORDS)
D016604:Aflatoxin B1; D000348:Aflatoxins / Q000378:metabolism* / Q000493:pharmacokinetics / Q000633:toxicity; D000818:Animals; D001571:Benzoflavones / Q000008:administration & dosage / Q000494:pharmacology*; D002083:Butylated Hydroxyanisole / Q000008:administration & dosage / Q000494:pharmacology*; D002273:Carcinogens / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D004247:DNA / Q000378:metabolism*; D004032:Diet; D005419:Flavonoids / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008113:Liver Neoplasms / Q000139:chemically induced* / Q000473:pathology; D012487:Salmonidae / Q000378:metabolism*; D014337:Trout / Q000378:metabolism*; D019324:beta-Naphthoflavone
D000348:Aflatoxins; D001571:Benzoflavones; D002273:Carcinogens; D005419:Flavonoids; D002083:Butylated Hydroxyanisole; D019324:beta-Naphthoflavone; D004247:DNA; D016604:Aflatoxin B1