EFFECTS OF NEPHROTOXIC COMPOUNDS ON RENAL- AND HEPATO-CARCINOGENESIS OF RATS
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Effects of nephrotoxic agents on rat hepato- and renal-carcinogenesis were examined histopathologically. Groups of male F344 rats were given a single intragastric administration of 400 mg/kg bw chloroform, 48 h after the treatment they were given 0.1% N-ethyl-N-hydroxyethylnitrosamine (EHEN) in drinking water for 2 weeks. One week after the withdrawal of EHEN treatment, 20 rats each were treated with 0.75% diphenylamine (DPA), 0.25% acetaminophen (AAP), 0.25% N-(3, 5-dichlorophenyl) succinimide (NDPS), 0.1% furocemide (FRM) in basal diet or basal diet alone for 31 weeks. Unilateral nephrectomy was carried out one week after the treatment with chemicals. Animals were killed for autopsy beginning 34 weeks after the treatment with EHEN.Histologically, the incidences of altered foci, neoplastic nodule, and hepatocellular carcinoma in the groups treated with DPA, AAP, NDPS or FRM were not significantly different from those of the controls. The incidence of microadenoma of the kidney in the group treated with DPA was significantly higher (P<0.01) than the control, but not different in other groups. The incidence of renal cell tumor was not modified by the additional treatment with nephrotoxic chemicals. These nephrotoxic chemicals did not induce any pathological changes in the liver and kidney at these dose levels employed in this experiment, except NDPS which induced mild interestitial nephritis. These results indicate that DPA has an enhancing effect on the renal carcinogenesis without inducing toxic changes in the kidney.
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日本毒性病理学会 | 論文
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