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

Toxicol Appl Pharmacol. 1988 Oct;96(1):93-100. doi: 10.1016/0041-008x(88)90251-7.

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

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

Substances

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