Concordance between Results of Medium-term Liver Carcinogenesis Bioassays and Long-term Findings for Carcinogenic 2-Nitropropane and Non-carcinogenic1-Nitropropane in F344 Rats |
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Authors: | Doi Yuko Tamano Seiko Kawabe Mayumi Sano Masashi Imai Norio Nakashima Hironao Furukawa Fumio Hagiwara Akihiro Otsuka Masanori Shirai Tomoyuki |
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Institution: | 1. DIMS Institute of Medical Science, Inc., 64 Goura, Nishiazai, Azai-cho, Ichinomiya 491-0113, Japan;2. Chemicals Evaluation and Research Institute, Japan, 1-4-25 Kouraku, Bunkyou-ku, Tokyo 112-0004, Japan;3. Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-ku, Mizuho-cho, Nagoya 467-8601, Japan;# Present: Chemicals Evaluation and Research Institute, Japan, 3-2-7 Miyanojin, Kurume 839-0801, Japan |
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Abstract: | This study was conducted to determine the concordance of results for a pair of structural
isomers, 2-nitropropane (2-NP) and 1-nitropropane (1-NP), using the rat medium-term liver
carcinogenesis bioassay (Ito test) and previously published long-term carcinogenicity
tests. Male F344 rats were given a single intraperitoneal injection of DEN (200?mg/kg
b.w.) to initiate hepatocarcinogenesis. After 2 weeks, they received per os 0, 0.8, 4 or
20?mg/kg/day of 2-NP or 1-NP six times a week and were subjected to two-thirds partial
hepatectomy at week 3. Non-initiated groups receiving 0 or 20?mg/kg/day were also
included. The animals were sacrificed for quantitative analysis of GST-P-positive foci at
week 8. With the highest dose of 2-NP, significantly increased numbers and areas of
GST-P-positive foci were demonstrated as compared with the respective control but were not
noted with 1-NP. In the non-DEN-initiated groups, many small GST-P-positive foci of less
than 0.2?mm in diameter were also induced in the rats treated with 2-NP at 20?mg/kg/day
but were lacking with 1-NP. These results strongly support that 2-NP is a complete
hepatocarcinogen with a potent initiation activity, whereas 1-NP is not. |
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Keywords: | the rat medium-term liver carcinogenesis bioassay Ito test 1-nitropropane 2-nitropropane |
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