High sensitivity of fatty liver Shionogi (FLS) mice to diethylnitrosamine hepatocarcinogenesis: comparison to C3H and C57 mice.
The fatty liver Shionogi (FLS) mouse is a new inbred strain that spontaneously develops fatty liver with infiltration of mononuclear cells. Moreover, this mouse is known to frequently develop spontaneous hepatic cancers. Recently, human non-alcholic steatohepatitis (NASH) has been focused of attention regarding hepatocellular carcinoma. Therefore, this mouse has potential as a model for human hepatic cancer due to steatosis. It is of interest therefore, whether it exhibits elevated susceptibility not only regarding spontaneous tumor development but also to chemical hepatocarcinogens. To examine this concern, we examined diethylnitrosamine (DEN) hepatocarcinogenesis in FLS mice with 30ppm in drinking water for 26 weeks in comparison to two other strains of mice, C3H and C57. The induction of spontaneous and DEN-induced hepatic tumors was clearly increased in the FLS case, along with levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker of oxidative DNA damage, as compared to the other strains, with or without DEN treatment. These results indicate that the oxidative DNA stress is intimately involved in hepatocarcinogenesis in FLS mice and provide further support for use of this mouse as a useful model for investigating hepatocarcinogenesis due to human hepatic steatosis.
First Department of Pathology, Osaka City University Medical School, 1-4-3 Asahi-Machi, Osaka, Japan.
Shuji
S
Iwai
Takashi
T
Murai
Susumu
S
Makino
Wei
W
Min
Keiichirou
K
Morimura
Satoru
S
Mori
Atsushi
A
Hagihara
Shuichi
S
Seki
Shoji
S
Fukushima
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000477:Alkylating Agents / Q000008:administration & dosage / Q000633:toxicity; D000818:Animals; D004247:DNA / Q000737:chemistry / Q000235:genetics; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000032:analysis; D004052:Diethylnitrosamine / Q000008:administration & dosage / Q000633:toxicity*; D018450:Disease Progression; D005234:Fatty Liver / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D013045:Species Specificity
D000477:Alkylating Agents; D018809:Proliferating Cell Nuclear Antigen; D004052:Diethylnitrosamine; D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; D003849:Deoxyguanosine