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.
Ogawa
K
K
First Department of Pathology, Nagoya City University Medical School, Japan.
Hasegawa
R
R
Wada
S
S
Yamaguchi
S
S
Ito
N
N
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