Effects of phenolic antioxidants in low dose combination on forestomach carcinogenesis in rats pretreated with N-methyl-N'-nitro-N-nitrosoguanidine.
The combined effects of low doses of promoters or carcinogens on two-stage forestomach carcinogenesis were examined in rats pretreated with N-methyl-N'-nitro-N-nitrosoguanidine. Groups of 15 rats were given a single 150 mg/kg body weight intragastric dose of N-methyl-N'-nitro-N-nitrosoguanidine. Starting 1 week later they were fed a diet containing low doses of known forestomach promoters/carcinogens (0.5% caffeic acid, 0.2% catechol, 0.5% butylated hydroxyanisole, or 0.25% 2-tert-butyl-4-methylphenol), alone or in combination, or basal diet without antioxidant supplement for 35 weeks. Histopathological examination revealed the incidences of forestomach squamous cell carcinomas in animals treated with N-methyl-N'-nitro-N-nitrosoguanidine followed by caffeic acid, catechol, butylated hydroxyanisole, 2-tert-butyl-4-methylphenol, and basal diet to be 27, 20, 13, 13, and 7%, respectively, whereas the incidence increased to 80% by the combined treatment with these four chemicals. The present results thus show that although the low doses of individual promoters/carcinogens did not have significant promoting activity, their combination exerted a strong enhancing influence on rat forestomach carcinogenesis. The findings indicate the importance of summation and synergism at a low dose for agents present in the human environment.
Hirose
M
M
First Department of Pathology, Nagoya City University Medical School, Nagoya, Japan.
Mutai
M
M
Takahashi
S
S
Yamada
M
M
Fukushima
S
S
Ito
N
N
D000818:Animals; D002083:Butylated Hydroxyanisole / Q000633:toxicity*; D002084:Butylated Hydroxytoluene / Q000633:toxicity* / Q000031:analogs & derivatives; D006965:Hyperplasia / Q000139:chemically induced; D008297:Male; D008769:Methylnitronitrosoguanidine; D011292:Premedication; D051381:Rats; D013270:Stomach / Q000473:pathology; D013274:Stomach Neoplasms / Q000139:chemically induced*
D008769:Methylnitronitrosoguanidine; D002084:Butylated Hydroxytoluene; D002083:Butylated Hydroxyanisole; C054527:2-tert-butyl-4-methylphenol