Modulation of diethylnitrosamine-induced hepatocarcinogenesis and O6-ethylguanine formation in rainbow trout by indole-3-carbinol, beta-naphthoflavone, and Aroclor 1254.

Abstract

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.

• Authors: A T Fong, J D Hendricks, R H Dashwood, S Van Winkle, B C Lee, G S Bailey
• Journal: Toxicology and applied pharmacology (Toxicol Appl Pharmacol) Vol. 96 Issue 1 Pg. 93-100 (Oct 1988) ISSN: 0041-008X [Print] United States
• PMID: 3142102 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Aroclors
• Benzoflavones
• Flavonoids
• Indoles
• Chlorodiphenyl (54% Chlorine)
• Diethylnitrosamine
• 6-ethylguanine
• Guanine
• beta-Naphthoflavone
• DNA
• indole-3-carbinol
• Polychlorinated Biphenyls

Topics

• Animals
• Aroclors (pharmacology)
• Benzoflavones (pharmacology)
• Chlorodiphenyl (54% Chlorine)
• Chromatography, High Pressure Liquid
• DNA (metabolism)
• Diethylnitrosamine (toxicity)
• Flavonoids (pharmacology)
• Guanine (analogs & derivatives, metabolism)
• Indoles (pharmacology)
• Liver (metabolism)
• Liver Neoplasms (chemically induced)
• Polychlorinated Biphenyls (pharmacology)
• Salmonidae (metabolism)
• Trout (metabolism)
• beta-Naphthoflavone