Dose-dependent Promoting Effects of Catechol on Glandular Stomach Carcinogenesis in BALB/c Mice Initiated with N-Methyl-N-nitrosourea |
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Authors: | Kiyoshi Kobayashi Nobuyuki Shimizu Tetsuya Tsukamoto Ken-ichi Inada Hayao Nakanishi Kazuhiro Goto Mamoru Mutai Masae Tatematsu |
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Affiliation: | Laboratory of Pathology, Aichi Cancer Center Research Institute, 1–1 Kanokoden, Chikusa-ku, Nagoya 464;Toxicology Laboratory, Life Science Research Sector, Mitsubishi Chemical Co. Yokohama Research Center, 1000 Kamoshida, Aoba-ku, Yokohama 227 |
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Abstract: | The effects of cateehol administration in the diet on stomach carcinogenesis in mice after initiation with N -methyl- N -nitrosourea (MNU) in the drinking water were investigated in a development trial for a new experimental protocol. Male 6-week-old BALB/c mice were given MNU in the drinking water intermittently for a total of three one-week periods, with one-week intervals, at the concentration of 120 ppm (groups 1 and 2). Groups 3 and 4 served as non initiated controls. From week 7, groups 1 and 3 were divided into three subgroups and the mice were fed on diet containing 0.05% (groups la and 3a), 0.2% (groups Ib and 3b), 0.8% (groups 1c and 3c) or 0% (groups 2 and 4) cateehol for 29 weeks. At week 20, appreciably enhanced development of pepsinogen 1-altered pyloric glands was noted in all catechol-treated groups, in a partially dose-dependent manner (12.8±12.5, 13.8±11.7, and 24.0±12.7/100 pyloric glands respectively, for groups 1, 2 and 3). The incidences of adenomas (groups 1, 2 and 3) were also increased. At week 35, dose-dependent induction of adenocarcinomas in groups 1 (3/19), 2 (3/19) and 3 (14/20) was evident. In addition, the depth of invasion of the adenocarcinomas was enhanced by cateehol in a dose-dependent manner, though the histological type was not influenced. Thus, the administration of cateehol in the diet strongly enhanced the pre-neoplastic and neoplastic lesions in mouse glandular stomach induced by MNU in the drinking water, in a dose-dependent manner |
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Keywords: | Catechol N-methyl-N-nitrosourea Pepsinogen I-altered pyloric gland Stomach cancer Mouse |
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