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Gene Expression Analysis on the Dicyclanil-Induced Hepatocellular Tumors in Mice
1 Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, Fuchu, Tokyo 183-8509, Japan Correspondence: Address correspondence to: Mitsuyoshi Moto, Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo 183-8509, Japan; e-mail:m-moto{at}cc.tuat.ac.jp Our previous studies showed the possibility that oxidative stress, including oxidative DNA damage, is involved in the mechanism of dicyclanil (DC)-induced hepatocarcinogenesis at the preneoplastic stage in mice. In this study, the expression analyses of genes, including oxidative stress-related genes, were performed on the tissues of hepatocellular tumors in a two-stage liver carcinogenesis model in mice. After partial hepatectomy, male ICR mice were injected with N-diethylnitrosamine (DEN) and given a diet containing 0 or 1500 ppm of DC for 20 weeks. Histopathological examinations revealed that the incidence of hepatocellular tumors (adenomas and carcinomas) significantly increased in the DEN + DC group. Gene expression analysis on the microdissected liver tissues of the mice in the DEN + DC group showed the highest expression levels of oxidative stress-related genes, such as Cyp1a1 and Txnrd1, in the tumor areas. However, no remarkable up-regulation of Ogg1—an oxidative DNA damage repair gene—was observed in the tumor areas, but the expression of Trail—an apoptosis-signaling ligand gene—was significantly down-regulated in the tumor tissues. These results suggest the possibility that the inhibition of apoptosis and a failure in the ability to repair oxidative DNA damage occur in the hepatocellular DC-induced tumors in mice.
Key Words: Chemical carcinogenesis • dicyclanil • liver • mouse • non-genotoxic carcinogen Abbreviations: 8-OHdG, 8-hydroxydeoxyguanosine • CYP, cytochrome P450 • DC, dicyclanil • DEN, N-diethylnitrosamine • FAO, Food and Agriculture Organization • GGT,
Toxicologic Pathology, Vol. 34, No. 6,
744-751 (2006) This article has been cited by other articles:
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-glutamyltransferase • Hmox1, heme oxygenase 1 • JECFA, Joint FAO/WHO Expert Committee on Food Additives • LCM, laser-capture microdissection • Ogg1, 8-oxoguanine DNA glycosylase • PB, phenobarbital • ROS, reactive oxygen species • TNF, tumor necrosis factor • Trail, TNF-related apoptosis-inducing ligand 10 • Txnrd1, thioredoxin reductase 1 • WHO, World Health Organization
