Hepatic cell loss and proliferation induced by N-2-fluorenylacetamide, diethylnitrosamine, and aflatoxin B1 in relation to hepatoma induction.
Three hepatic carcinogens (aflatoxin B1, diethylnitrosamine (DEN) and N-2-fluorenylacetamide (FAA)) were compared for carcinogenicity, early cell toxicity and parenchymal cell proliferation. The carcinogens were administered to rats for 15 weeks as follows: aflatoxin B1, 1 in 10(6) in pelleted food; DEN, 2 in 10(5) in drinking water; FAA, 3 in 10(4) in pelleted food. The loss of prelabelled DNA and the [H3] TdR pulse-labelling indices (LI) of parenchymal and nonparenchymal cells were determined at various times during the period of carcinogen availability. On a molar basis, aflatoxin B1 was 90 times as carcinogenic as FAA and 24 times as carcinogenic as DEN. However, for about equal magnitudes of hepatic cell proliferation and loss, aflatoxin B1 was the least potent carcinogen. For a given level of carcinogenicity, FAA was more potent than DEN in causing loss of hepatic DNA and in increasing the parenchymal cell labelling index. DEN and aflatoxin B1 produced about the same degree of DNA loss and parenchymal cell labelling, but the former was a more potent carcinogen. When carcinogenicity was compared for approximately equal levels of early hepatic cell destruction and proliferation, the 3 chemicals in the present study could be ranked in descending order of potency as DEN, FAA and aflatoxin B1.
D015073:2-Acetylaminofluorene / Q000633:toxicity*; D000348:Aflatoxins / Q000633:toxicity*; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000139:chemically induced* / Q000473:pathology; D002455:Cell Division; D004247:DNA / Q000378:metabolism; D004052:Diethylnitrosamine / Q000633:toxicity*; D005449:Fluorenes / Q000633:toxicity*; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008113:Liver Neoplasms / Q000139:chemically induced* / Q000473:pathology; D008297:Male; D009602:Nitrosamines / Q000633:toxicity*; D051381:Rats; D013997:Time Factors
D000348:Aflatoxins; D005449:Fluorenes; D009602:Nitrosamines; D004052:Diethylnitrosamine; D004247:DNA; D015073:2-Acetylaminofluorene