Concordance between Results of Medium-term Liver Carcinogenesis Bioassays and Long-term Findings for Carcinogenic 2-Nitropropane and Non-carcinogenic 1-Nitropropane in F344 Rats

Yuko Doi; Seiko Tamano; Mayumi Kawabe; Masashi Sano; Norio Imai; Hironao Nakashima; Fumio Furukawa; Akihiro Hagiwara; Masanori Otsuka; Tomoyuki Shirai

doi:10.1293/tox.24.207

Originals

Concordance between Results of Medium-term Liver Carcinogenesis Bioassays and Long-term Findings for Carcinogenic 2-Nitropropane and Non-carcinogenic 1-Nitropropane in F344 Rats

Yuko Doi, Seiko Tamano, Mayumi Kawabe, Masashi Sano, Norio Imai, Hironao Nakashima, Fumio Furukawa, Akihiro Hagiwara, Masanori Otsuka, Tomoyuki Shirai

Author information

Yuko Doi
DIMS Institute of Medical Science, Inc., 64 Goura, Nishiazai, Azai-cho, Ichinomiya 491-0113, Japan
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
Seiko Tamano
DIMS Institute of Medical Science, Inc., 64 Goura, Nishiazai, Azai-cho, Ichinomiya 491-0113, Japan
Mayumi Kawabe
DIMS Institute of Medical Science, Inc., 64 Goura, Nishiazai, Azai-cho, Ichinomiya 491-0113, Japan
Masashi Sano
DIMS Institute of Medical Science, Inc., 64 Goura, Nishiazai, Azai-cho, Ichinomiya 491-0113, Japan
Norio Imai
DIMS Institute of Medical Science, Inc., 64 Goura, Nishiazai, Azai-cho, Ichinomiya 491-0113, Japan
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
Hironao Nakashima
DIMS Institute of Medical Science, Inc., 64 Goura, Nishiazai, Azai-cho, Ichinomiya 491-0113, Japan
Fumio Furukawa
DIMS Institute of Medical Science, Inc., 64 Goura, Nishiazai, Azai-cho, Ichinomiya 491-0113, Japan
Akihiro Hagiwara
DIMS Institute of Medical Science, Inc., 64 Goura, Nishiazai, Azai-cho, Ichinomiya 491-0113, Japan
Masanori Otsuka
Chemicals Evaluation and Research Institute, Japan, 1-4-25 Kouraku, Bunkyou-ku, Tokyo 112-0004, Japan
Present: Chemicals Evaluation and Research Institute, Japan, 3-2-7 Miyanojin, Kurume 839-0801, Japan
Tomoyuki Shirai
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

Keywords: the rat medium-term liver carcinogenesis bioassay, Ito test, 1-nitropropane, 2-nitropropane

JOURNAL FREE ACCESS

2011 Volume 24 Issue 4 Pages 207-213

DOI https://doi.org/10.1293/tox.24.207

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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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