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

摘要

This study was conducted to determine the concordance of results for a pair of structuralisomers, 2-nitropropane (2-NP) and 1-nitropropane (1-NP), using the rat medium-term livercarcinogenesis bioassay (Ito test) and previously published long-term carcinogenicitytests. Male F344 rats were given a single intraperitoneal injection of DEN (200 mg/kgb.w.) to initiate hepatocarcinogenesis. After 2 weeks, they received per os 0, 0.8, 4 or20 mg/kg/day of 2-NP or 1-NP six times a week and were subjected to two-thirds partialhepatectomy at week 3. Non-initiated groups receiving 0 or 20 mg/kg/day were alsoincluded. The animals were sacrificed for quantitative analysis of GST-P-positive foci atweek 8. With the highest dose of 2-NP, significantly increased numbers and areas ofGST-P-positive foci were demonstrated as compared with the respective control but were notnoted with 1-NP. In the non-DEN-initiated groups, many small GST-P-positive foci of lessthan 0.2 mm in diameter were also induced in the rats treated with 2-NP at 20 mg/kg/daybut were lacking with 1-NP. These results strongly support that 2-NP is a completehepatocarcinogen with a potent initiation activity, whereas 1-NP is not.