Influence of the nature and the dose of the initiator on the development of premalignant and malignant lesions in rat hepatocarcinogenesis.
Using a triphasic protocol recently described to induce malignant tumors in rat liver, the question has been asked whether both the nature and the dose of the initiator influence the carcinogenic process. Two nitrosamines (diethylnitrosamine DEN and N-nitrosomorpholine NNM) have been used to initiate that process. With regard to the premalignant stages appearing in the liver up to 19 weeks after initiation, there is a dose-dependent relationship between the dose of initiator and both the percentage of the parenchyma occupied by and the number of GGT+ lesions. DEN is always more potent than equivalent doses of NNM. With regard to malignant tumors appearing within the period of observation (up to 44 weeks), the two highest doses (100 and 200 mg/kg) of DEN appear to be the only carcinogenic treatments. Cancer incidence (percentage of rats bearing histologically characterized malignant tumor) is the same after both treatments, but the tumor yield (number of tumors per rat bearing macroscopic tumors) is higher (+/- 2X) after 200 mg/kg than after 100 mg/kg.
D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D004052:Diethylnitrosamine / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D008099:Liver / Q000187:drug effects / Q000473:pathology*; D008114:Liver Neoplasms, Experimental / Q000473:pathology*; D008297:Male; D009602:Nitrosamines / Q000633:toxicity*; D011230:Precancerous Conditions / Q000139:chemically induced / Q000473:pathology*; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D002273:Carcinogens; D009602:Nitrosamines; D004052:Diethylnitrosamine; C002741:N-nitrosomorpholine