Gene expression analysis on the dicyclanil-induced hepatocellular tumors in mice.
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.
Moto
Mitsuyoshi
M
Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, Fuchu, 183-8509 Tokyo, Japan. m-moto@cc.tuat.ac.jp
Okamura
Miwa
M
Muguruma
Masako
M
Ito
Tadasi
T
Jin
Meilan
M
Kashida
Yoko
Y
Mitsumori
Kunitoshi
K
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001835:Body Weight / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000139:chemically induced / Q000235:genetics / Q000473:pathology*; D003043:Cocarcinogenesis; D045643:DNA Repair Enzymes / Q000235:genetics; D004052:Diethylnitrosamine; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006498:Hepatectomy; D007605:Juvenile Hormones / Q000633:toxicity; D007834:Lasers; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000235:genetics / Q000473:pathology*; D008297:Male; D053858:Metabolic Networks and Pathways / Q000235:genetics; D051379:Mice; D008813:Mice, Inbred ICR; D042282:Microdissection / Q000379:methods; D020411:Oligonucleotide Array Sequence Analysis; D018384:Oxidative Stress / Q000235:genetics; D011230:Precancerous Conditions / Q000139:chemically induced / Q000235:genetics / Q000473:pathology*; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction
D007605:Juvenile Hormones; D004052:Diethylnitrosamine; C121718:dicyclanil; D045643:DNA Repair Enzymes