Modifying Effects of Various Chemicals on Tumor Development in a Rat Wide‐spectrum Organ Carcinogenesis Model

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.