Dose response study of N-nitrosodiethanolamine initiation of rat hepatocarcinogenesis.
Initiating activity of N-nitrosodiethanolamine (NDELA) for rat liver carcinogenesis was investigated using an 8-weeks bioassay system. Male F344 rats were initially treated with a single intraperitoneal injection of NDELA at one of five dose levels: 1,600, 800, 400, 200, or 100 mg/kg. Two weeks later, the rats were placed on 0.02% 2-acetylaminofluorene (2-AAF) or 0.05% phenobarbital (PB) containing diet for 6 weeks. All animals were subjected to 2/3 partial hepatectomy 4 weeks after the NDELA treatment, and killed at the end of the eighth week. NDELA itself exerted low toxicity in terms of body weight gain. Clear dose-dependent initiating activity of NDELA was observed in terms of development of glutathione S-transferase placental form (GST-P) positive liver cell foci, this being more apparent with PB promotion than with 2-AAF where the enhancing regimen itself caused multiple lesion development. Initiating potential of NDELA, however, was much lower than that observed for diethylnitrosamine in our previous work.
First Department of Pathology, Nagoya City University Medical School, Japan.
K
K
Ogawa
R
R
Hasegawa
S
S
Wada
S
S
Yamaguchi
N
N
Ito
D015073:2-Acetylaminofluorene; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D056486:Chemical and Drug Induced Liver Injury; D003043:Cocarcinogenesis; D004052:Diethylnitrosamine / Q000008:administration & dosage / Q000633:toxicity* / Q000031:analogs & derivatives; D004305:Dose-Response Relationship, Drug; D005982:Glutathione Transferase / Q000032:analysis; D006498:Hepatectomy; D007274:Injections, Intraperitoneal; D008099:Liver / Q000473:pathology; D008107:Liver Diseases / Q000201:enzymology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced*; D008115:Liver Regeneration; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010634:Phenobarbital; D011230:Precancerous Conditions / Q000139:chemically induced / Q000201:enzymology; D051381:Rats; D011916:Rats, Inbred F344
C014129:N-nitrosodiethanolamine; D004052:Diethylnitrosamine; D015073:2-Acetylaminofluorene; D005982:Glutathione Transferase; D010634:Phenobarbital