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- Title
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.
- Authors
Doi, Yuko; Tamano, Seiko; Kawabe, Mayumi; Sano, Masashi; Imai, Norio; Nakashima, Hironao; Furukawa, Fumio; Hagiwara, Akihiro; Otsuka, Masanori; Shirai, Tomoyuki
- 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.
- Subjects
CARCINOGENESIS; LIVER cancer; BIOLOGICAL assay; NITROPROPANE; LABORATORY rats; HEPATECTOMY; QUANTITATIVE research
- Publication
Journal of Toxicologic Pathology, 2011, Vol 24, Issue 4, p207
- ISSN
0914-9198
- Publication type
Article
- DOI
10.1293/tox.24.207