Modifying effects of various chemicals on tumor development in a rat wide-spectrum organ carcinogenesis model

Jpn J Cancer Res. 1992 Aug;83(8):812-20. doi: 10.1111/j.1349-7006.1992.tb01985.x.

Abstract

The efficacy of a wide-spectrum organ carcinogenesis model for detection of modification potential of exogenous agents was investigated in F344 male rats. Groups of animals were sequentially injected with N-bis(2-hydroxypropyl)nitrosamine (1000 mg/kg body weight, i.p., in saline, twice in week 1), N-ethyl-N-hydroxyethylnitrosamine (1500 mg/kg body weight, i.g., in distilled water, twice in week 2) and 3,2'-dimethyl-4-aminobiphenyl (75 mg/kg body weight, s.c., in corn oil, twice in week 3) for wide-spectrum initiation of target organs and then given one of 10 test chemicals, comprising 6 hepatocarcinogens and 4 non-hepatocarcinogens, for 12 weeks. All 10 chemicals exerted modifying effects in their respective target organs. Enhancing influence could be detected in the liver and urinary bladder with 2-acetylaminofluorene, ethionine, and 3'-methyl-4-dimethylaminoazobenzene; in the liver and thyroid with 4,4'-diaminodiphenylmethane and phenobarbital; in the esophagus and urinary bladder with N-butyl-N-(4-hydroxybutyl)nitrosamine; in the forestomach and urinary bladder with butylated hydroxyanisole; in the liver with 7,12-dimethylbenz[a]anthracene and in the liver and lung with 3-methylcholanthrene. Inhibitory effects on development of glutathione S-transferase placental form-positive liver cell foci were observed with clofibrate. The results indicate that the present model can be reliably utilized as a whole body medium-term bioassay system for assessment of environmental cancer modifiers.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Weight / drug effects
  • Carcinogenicity Tests
  • Carcinogens / toxicity*
  • Drinking Behavior / drug effects
  • Esophageal Neoplasms / chemically induced
  • Esophageal Neoplasms / pathology
  • Feeding Behavior / drug effects
  • Liver Neoplasms / chemically induced
  • Liver Neoplasms / pathology
  • Liver Neoplasms, Experimental / chemically induced
  • Lung Neoplasms / chemically induced
  • Lung Neoplasms / pathology
  • Male
  • Neoplasms, Experimental / chemically induced*
  • Neoplasms, Experimental / pathology
  • Organ Specificity
  • Rats
  • Rats, Inbred F344
  • Urinary Bladder Neoplasms / chemically induced
  • Urinary Bladder Neoplasms / pathology

Substances

  • Carcinogens