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.
Uwagawa
S
S
First Department of Pathology, Nagoya City University Medical School.
Tsuda
H
H
Ozaki
K
K
Takahashi
S
S
Yamaguchi
S
S
Mutai
M
M
Aoki
T
T
Ito
N
N
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D015197:Carcinogenicity Tests; D002273:Carcinogens / Q000633:toxicity*; D004327:Drinking Behavior / Q000187:drug effects; D004938:Esophageal Neoplasms / Q000139:chemically induced / Q000473:pathology; D005247:Feeding Behavior / Q000187:drug effects; D008113:Liver Neoplasms / Q000139:chemically induced / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced; D008175:Lung Neoplasms / Q000139:chemically induced / Q000473:pathology; D008297:Male; D009374:Neoplasms, Experimental / Q000139:chemically induced* / Q000473:pathology; D009928:Organ Specificity; D051381:Rats; D011916:Rats, Inbred F344; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced / Q000473:pathology
D002273:Carcinogens