Hepatocarcinogenic susceptibility of rasH2 mice to troglitazone in a two-stage hepatocarcinogenesis model.
Six-week-old rasH2 mice were injected intraperitoneally with N-diethylnitrosamine (DEN) after partial hepatectomy and administrated 0 or 6,000 ppm troglitazone (TRG) for 10 weeks. Relative liver weight of females increased significantly in the DEN + TRG group compared to the DEN-alone group. The numbers of gamma-glutamyltranspeptidase- and proliferating cell nuclear antigen (PCNA)-positive cells tended to increase in both the sexes in the DEN + TRG group; however, these changes were not significantly different from those in the DEN-alone group. Levels of gene expressions for vascular endothelial growth factor (VEGF) and VEGFB (related to angiogenesis), tropomyosin 1 (Tpm1) and transforming growth factor-beta (related to ras/MAPK cascade activation), and PCNA (related to cell proliferation) in females were significantly higher in the DEN + TRG than in the untreated control group but not in the DEN-alone group. Only Tpm1 gene had significantly higher expression in the DEN + TRG group than in the DEN-alone group. These results suggest that rasH2 mice are not susceptible to TRG in a two-stage hepatocarcinogenesis model.
Jin
Meilan
M
Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo 183-8509, Japan. meilan@cc.tuat.ac.jp
Saekusa
Yukie
Y
Dewa
Yasuaki
Y
Nishimura
Jihei
J
Matsumoto
Sayaka
S
Shibutani
Makoto
M
Hasumi
Keiji
K
Mitsumori
Kunitoshi
K
D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D002273:Carcinogens / Q000633:toxicity*; D002839:Chromans / Q000633:toxicity*; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D004305:Dose-Response Relationship, Drug; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D007150:Immunohistochemistry; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced* / Q000235:genetics* / Q000473:pathology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009929:Organ Size / Q000187:drug effects; D011230:Precancerous Conditions / Q000139:chemically induced* / Q000235:genetics* / Q000473:pathology; D016019:Survival Analysis; D045162:Thiazolidinediones / Q000633:toxicity*; D013997:Time Factors; D000077288:Troglitazone; D005723:gamma-Glutamyltransferase / Q000378:metabolism
D014408:Biomarkers, Tumor; D002273:Carcinogens; D002839:Chromans; D045162:Thiazolidinediones; D005723:gamma-Glutamyltransferase; D000077288:Troglitazone