ISSN:
0730-2312
Keywords:
hepatocarcinogenesis
;
initiation
;
promotion
;
neoplasm
;
altered-cell island
;
Life and Medical Sciences
;
Cell & Developmental Biology
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
Notes:
We have quantified the initiation of hepatocytic neoplasms and the induction of altered cell islands in regenerating livers of rats given a single treatment with one of three carcinogens before or during the peak of DNA synthesis after partial hepatectomy. For up to 20 wk after treating livers during the peak of DNA synthesis with methyl(acetoxymethy1)nitrosamine (DMN-Ac), hepatocytic neoplasms were not seen. Thereafter, in rats fed the liver tumor promoter, phenobar-bital, neoplasms emerged continuously so that by 60 wk after initiation, livers held an average of 5.5 neoplasms. Islands of cellular alteration, identified by their abnormal retention of glycogen on fasting, also appeared to emerge continuously between 20 and 60 wk after initiation. By 60 wk, promoted livers contained about 10,000 islands. In DMN-Ac-initiated, phenobarbital-promoted livers, neoplasms and islands maintained a constant numerical relationship over time with about 1,450 islands emerging for every neoplasm that emerged. This ratio of islands to neoplasms differed according to the type of carcinogen used to initiate hepatocar-cinogenesis and depending on whether promotion with phenobarbital was included. In livers initiated with DMN-Ac but not promoted with phenobarbital, the ratio of islands to neoplasms was about 7,750: 1. In livers initiated by treatment with (±)-7α,8β-dihydroxy-9β,10β-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene at the peak of DNA synthesis and then promoted with phenobarbital, the ratio of islands to neoplasms was 7,200: 1. In livers exposed to gamma rays at the peak of DNA synthesis in regenerating livers and promoted, no neoplasms were seen in our sample although islands could be enumerated. Evaluation of another group of rats irradiated during the prereplicative phase of regeneration revealed two neoplasms in nine treated livers and a ratio of islands to neoplasms of greater than 12,000: 1. Thus, when comparing livers treated once with carcinogen and then promoted, this ratio of islands to neoplasms differed considerably according to the carcinogen being tested. These results suggest that the induction of glycogen-retaining hepatocyte islands may not be a quantitative measure of the initiation of hepatocarcinogenesis.
Additional Material:
3 Ill.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1002/jcb.240300102
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