title: Comparison of the promoting effects of various agents in induction of preneoplastic lesions in rat liver.
abstract: The promoting activities of 29 compounds on induction of hyperplastic (neoplastic) liver nodules (HN) and the dose-dependent effects of tumor promoting agents were compared by using a short-term test system developed in this laboratory. In tests on promoting activity, F344 rats were given a single dose (200 mg/kg) of N-nitrosodiethylamine (DEN), and from two weeks later, were treated with various test compounds for 6 or 10 weeks. They were subjected to partial hepatectomy 3 or 4 weeks after DEN treatment. The results showed that strong hepatocarcinogens, such as aflatoxin B1, DEN, N-nitrosodimethylamine (DMN), 2-acetylaminofluorene (2-AAF), 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB) and ethionine, induced many hyperplastic liver nodules, whereas dieldrin, 1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane (DDT), polychlorinated biphenyls (PCB) and alpha-hexachlorocyclohexane (alpha-HCH) induced few lesions. Nonhepatocarcinogens, such as N-nitrosoethylurea (ENU) and 3-methylcholanthrene (3-MC), only slightly induced hyperplastic nodules. Of the miscellaneous compounds tested, phenobarbital, deoxycholic acid and ethynyl estradiol also induced gamma-glutamyl transpeptidase (gamma-GT) positive foci. In tests on the dose-dependent effects of promoting agents, DMN was given at different concentrations for 6 weeks from 2 weeks after DEN treatment. Results were quantitated by histochemical measurement of the number or area of gamma-GT positive lesions induced. A long-term experiment on the effect of feeding DMN for 96 weeks was also done. Clear dose-dependent effects of DMN were seen in induction of gamma-GT positive foci in the short-term experiment and neoplastic lesions in the long-term one.
mesh_terms: D015073:2-Acetylaminofluorene; D000818:Animals; D002273:Carcinogens; D003043:Cocarcinogenesis; D004052:Diethylnitrosamine; D004305:Dose-Response Relationship, Drug; D001556:Hexachlorocyclohexane; D008113:Liver Neoplasms / Q000139:chemically induced*; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced*; D011230:Precancerous Conditions / Q000139:chemically induced*; D051381:Rats; D005723:gamma-Glutamyltransferase / Q000378:metabolism
chemical_list: D002273:Carcinogens; D004052:Diethylnitrosamine; D001556:Hexachlorocyclohexane; D015073:2-Acetylaminofluorene; D005723:gamma-Glutamyltransferase