title: Promotion of spontaneous preneoplastic cells in rat liver as a possible explanation of tumor production by nonmutagenic compounds.
abstract: Foci of putative preneoplastic cells were detected in the livers of untreated aged Wistar rats of both sexes. The foci exhibited markers similar to those of their counterparts in carcinogen-treated rats such as increased cytoplasmic basophilia, clearness of cytoplasm, or expression of gamma-glutamyltransferase. Rates of DNA synthesis in foci were higher than in normal liver and were further increased by single doses of liver mitogens assumed to promote liver tumor development (phenobarbital, alpha-hexachlorocyclohexane, cyproterone acetate, nafenopin). Thus, cells in the spontaneous foci appear to possess a defect in growth control, rendering them more susceptible to endogenous and exogenous growth stimuli. This defect has been found previously in carcinogen-induced foci and may be used as a marker for putative preneoplastic cells. The spontaneous foci are present at low incidence in 8-month-old rats; at 2 years, all of 50 rats studied possessed foci. These observations suggest that nongenotoxic compounds can produce liver tumors if they promote tumor development from preneoplastic foci. Therefore, long-term bioassay for carcinogenicity will not discriminate between initiating and promoting compounds if preneoplastic lesions develop in control animals.
mesh_terms: D000375:Aging; D000818:Animals; D002273:Carcinogens / Q000494:pharmacology; D004261:DNA Replication / Q000187:drug effects; D005260:Female; D008099:Liver / Q000254:growth & development / Q000473:pathology; D008113:Liver Neoplasms / Q000139:chemically induced* / Q000473:pathology; D008297:Male; D009374:Neoplasms, Experimental / Q000473:pathology / Q000503:physiopathology; D011230:Precancerous Conditions / Q000473:pathology / Q000503:physiopathology*; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D002273:Carcinogens