Initiation-promotion-initiation. Induction of neoplastic foci within islands of precancerous liver cells in the rat.
The hypothesis that during the promotion phase of carcinogenesis a second rare event leads to a promoter-independent tumour cell was tested in an initiation-promotion-initiation type of experiment. Precancerous (island) cells induced in rat liver by 10 mg/kg N-nitrosodiethylamine given 24 h after partial hepatectomy were promoted by a protocol consisting of 2-acetylaminofluorene/partial hepatectomy. Administration of 25-100 mg/kg N-ethyl-N-nitrosourea served as second initiater. Microscopic foci of neoplastic cells were observed within the precancerous islands 66 days later; no such foci were noted in the appropriate controls. Deficiency of adenosine triphosphatase and glucose-6-phosphatase marker enzymes in the foci was more pronounced than in the surrounding island cells; glycogen storage was decreased and cytoplasmic basophilia slightly increased; gamma-glutamyltranspeptidase staining was negative or decreased with respect to the surrounding island cells, which exhibited a partially positive reaction. We conclude that a secondary change produced by N-ethyl-N-nitrosourea in precancerous island cells leads to focus-forming cells which grow, in the absence of promoter, into foci of neoplastic phenotype. Similar rare, initiation-like events might be involved in the process of tumour promotion in general.
D015073:2-Acetylaminofluorene / Q000633:toxicity*; D000818:Animals; D004052:Diethylnitrosamine / Q000633:toxicity*; D005038:Ethylnitrosourea / Q000633:toxicity*; D005260:Female; D006498:Hepatectomy; D008099:Liver / Q000187:drug effects / Q000473:pathology*; D008113:Liver Neoplasms / Q000139:chemically induced* / Q000473:pathology; D008115:Liver Regeneration / Q000187:drug effects; D009602:Nitrosamines / Q000633:toxicity*; D009607:Nitrosourea Compounds / Q000633:toxicity*; D011230:Precancerous Conditions / Q000473:pathology*; D051381:Rats; D011919:Rats, Inbred Strains
D009602:Nitrosamines; D009607:Nitrosourea Compounds; D004052:Diethylnitrosamine; D015073:2-Acetylaminofluorene; D005038:Ethylnitrosourea