Histogenesis and the role of p53 and K-ras mutations in hepatocarcinogenesis by glyceryl trinitrate (nitroglycerin) in male F344 rats

Carcinogenesis
S TamanoJ M Rice

Abstract

Glyceryl trinitrate (GTN) was previously reported to induce hepatocellular carcinoma (HCC) in rats after prolonged feeding. The present experiments were undertaken to evaluate the histogenesis and molecular biology of these tumors and the possible role of nitric oxide (NO), a GTN metabolite, in their development. Male F344 rats received a single i.g. intubation of GTN (1.2 g/kg) at 6 weeks of age and/or a diet containing 1% GTN from 8 weeks of age until necropsy, i.e. for up to 78 weeks. Some animals were subjected to 2/3 partial hepatectomy (PH) at 9 weeks of age. Five sequential sacrifices (14, 32, 52, 78 and 84 weeks of age) were performed. No liver tumors developed in control rats or in rats that received GTN only by a single i.g. intubation, even when intubation was followed by PH. Preneoplastic foci, mainly of clear cell and mixed cell type (identified as positive for glutathione S-transferase placental form) were found from 14 weeks of age in rats receiving GTN in the diet. Focal eosinophilic areas (atypical foci) composed of atypical hepatocytes that often extended into the veins were observed beginning at 52 weeks of age. Some mixed hepatocholangiocellular adenomas and carcinomas arose in eosinophilic lesions. HCCs wer...Continue Reading

Citations

Jun 26, 1998·Mutation Research·W LinZ Zhou
May 22, 2001·Environmental Health Perspectives·W C GelderblomD Ramljak
Oct 5, 2011·Mutation Research·Giovanni BrambillaAntonietta Martelli
Oct 11, 2008·Mutation Research·Giovanni Brambilla, Antonietta Martelli
Apr 20, 2000·Redox Report : Communications in Free Radical Research·A RahmanM Athar
Jul 20, 1999·Molecular Carcinogenesis·M Gómez-AngelatsH C Pitot
Nov 6, 2020·Biochemical Society Transactions·Amir M AlsharabasyAbhay Pandit

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