title: Dose-related induction of hepatic preneoplastic lesions by diethylnitrosamine in C57BL/6 mice.
abstract: The C57BL/6 mouse strain (or derivation of this strain) is used as a background for many transgenic mouse models. This strain has a relatively low susceptibility to chemically induced hepatocarcinogenesis compared with other commonly used experimental mouse strains. In the present study, the authors treated C57BL/6 mice with 25, 50, and 75 mg/kg of diethylnitrosamine (DEN) for 4 or 8 weeks by intraperitoneal injection to investigate the dose-response pattern of preneoplastic and neoplastic lesion formation in the liver. DEN induced preneoplastic lesions and cytokeratin 8/18-positive foci in a dose-dependent manner. In the 75 mg/kg for 8 weeks treatment group, hepatocellular adenoma, cholangioma and hemangioma, and cytokeratin 19-positive foci were also induced, but a significant decrease in body weight was observed. The suitable DEN treatment range for this strain was concluded to be from 75 mg/kg for 4 weeks (total amount = 300 mg/kg) to 50 mg/kg for 8 weeks (total amount = 400 mg/kg). These results should prove useful for future studies investigating hepatocarcinogenesis in both the background C57BL/6 strain and other transgenic mouse models derived from it.
authors.affiliation: Department of Environmental Health, School of Public Health, Indiana University, Bloomington, IN 47405, USA.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Kushida
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Kamendulis
authors.forename: Tyler J
authors.initials: TJ
authors.lastname: Peat
authors.forename: James E
authors.initials: JE
authors.lastname: Klaunig
mesh_terms: D000818:Animals; D015197:Carcinogenicity Tests / Q000379:methods*; D004052:Diethylnitrosamine / Q000008:administration & dosage / Q000633:toxicity*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007150:Immunohistochemistry; D053539:Keratin-19 / Q000378:metabolism; D008099:Liver / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009929:Organ Size / Q000187:drug effects; D011230:Precancerous Conditions / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D011897:Random Allocation
chemical_list: D053539:Keratin-19; D004052:Diethylnitrosamine