Modulation of diethylnitrosamine-induced hepatocarcinogenesis and O6-ethylguanine formation in rainbow trout by indole-3-carbinol, beta-naphthoflavone, and Aroclor 1254.
Rainbow trout were fed a diet containing indole-3-carbinol (2000 ppm), beta-naphthoflavone (500 ppm), or Aroclor 1254 (100 ppm) for 6 weeks before a single 24-hr exposure to an aqueous solution of 250 ppm diethylnitrosamine (DEN). The fish were killed 42 weeks later to determine the carcinogenic response. DEN exposure produced an 80.2% incidence of liver tumors and an average of 3.47 tumors per tumor-bearing fish, whereas no tumors were detected in the sham-treated control fish. Tumor induction was inhibited by indole-3-carbinol (27.5% incidence, 1.89 tumors per tumor-bearing fish) but enhanced by beta-naphthoflavone (91.8% incidence, 3.60 tumors per tumor-bearing fish). Aroclor 1254 had no effect on DEN-induced hepatocarcinogenesis (80.0% incidence, 3.03 tumors per tumor-bearing fish). The effects of these modulators on O6-ethylguanine and 7-ethylguanine formation (measured by HPLC and fluorescence spectrophotometry) were examined. Liver DNA ethylguanine levels were reduced in indole-3-carbinol-pretreated fish and increased in beta-naphthoflavone-pretreated fish compared to untreated controls after DEN exposure. Aroclor 1254 pretreatment had no significant effect on DNA ethylguanine formation. Similar O6-ethylguanine to 7-ethylguanine ratios were found among the control and treated groups. The results of this study indicate that modulation of DEN hepatocarcinogenesis by indole-3-carbinol and beta-naphthoflavone may be mediated by their effects on O6-ethylguanine formation and, therefore, on the initiation phase of carcinogenesis.
D000818:Animals; D001140:Aroclors / Q000494:pharmacology*; D001571:Benzoflavones / Q000494:pharmacology*; D020111:Chlorodiphenyl (54% Chlorine); D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000378:metabolism; D004052:Diethylnitrosamine / Q000633:toxicity*; D005419:Flavonoids / Q000494:pharmacology*; D006147:Guanine / Q000031:analogs & derivatives* / Q000378:metabolism; D007211:Indoles / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism; D008113:Liver Neoplasms / Q000139:chemically induced*; D011078:Polychlorinated Biphenyls / Q000494:pharmacology*; D012487:Salmonidae / Q000378:metabolism*; D014337:Trout / Q000378:metabolism*; D019324:beta-Naphthoflavone
D001140:Aroclors; D001571:Benzoflavones; D005419:Flavonoids; D007211:Indoles; D020111:Chlorodiphenyl (54% Chlorine); D004052:Diethylnitrosamine; C007673:6-ethylguanine; D006147:Guanine; D019324:beta-Naphthoflavone; D004247:DNA; C016517:indole-3-carbinol; D011078:Polychlorinated Biphenyls