Gene Expression Analysis on the Dicyclanil-Induced Hepatocellular Tumors in Mice

• Published in: Toxicologic pathology 2006-10, Vol.34 (6), p.744-751
• Main Authors: Moto, Mitsuyoshi, Okamura, Miwa, Muguruma, Masako, Ito, Tadasi, Jin, Meilan, Kashida, Yoko, Mitsumori, Kunitoshi
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis - genetics; Body Weight - drug effects; Carcinoma, Hepatocellular - chemically induced; Carcinoma, Hepatocellular - genetics; Carcinoma, Hepatocellular - pathology; Cocarcinogenesis; Diethylnitrosamine; DNA Repair Enzymes - genetics; Gene Expression Profiling; Gene Expression Regulation, Neoplastic - drug effects; Hepatectomy; Juvenile Hormones - toxicity; Lasers; Liver - drug effects; Liver - pathology; Liver Neoplasms, Experimental - chemically induced; Liver Neoplasms, Experimental - genetics; Liver Neoplasms, Experimental - pathology; Male; Metabolic Networks and Pathways - genetics; Mice; Mice, Inbred ICR; Microdissection - methods; Oligonucleotide Array Sequence Analysis; Oxidative Stress - genetics; Precancerous Conditions - chemically induced; Precancerous Conditions - genetics; Precancerous Conditions - pathology; Reproducibility of Results; Reverse Transcriptase Polymerase Chain Reaction
• ISSN: 0192-6233; 1533-1601
• DOI: 10.1080/01926230600932471

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.