[The effect of the alkylating carcinogen dipin on the proliferation, the level of polyploidy development and on micronucleus formation in a population of parent and newly formed hepatocytes].
In the process of hepatocarcinogenesis induced by dipin and partial hepatectomy in mice, initial hepatocytes are gradually replaced with a population of newly formed hepatocytes which originate from oval cells (Radaeva, Factor, 1990). It has been shown that the increase in hepatocarcinogenesis duration (2-11 weeks) along with the intensification of oval-cell reaction are accompanied by a progressive injury of cell genome in the initial hepatocyte population. This injury manifests itself by an accumulation of cells with micronuclei as well as by the development of high levels of polyploidy and aneuploidy. In the initial parenchyma, clastogenic and aneuploidizing effects of dipin are maximally pronounced at the stage of appearing hepatocyte nodules which consist of newly formed hepatocytes (8-11 weeks). By this time the proliferative pool comprises 83-92%, the amount of aberrant cells increases in average from 7 to 50%, and the indices of average nuclear ploidy in population enhance 6-8 times as compared with the average level of polyploidy in normal parenchyma. The quota of binuclear cells without micronuclei abruptly falls while the quota of binuclear cells with micronuclei and nuclear bridges increases reaching 3/4 of the total amount of binuclear cells. Binuclear cells with nuclear bridges comprise about one third of binuclear cells with micronuclei. At the stage of hepatocytic nodules (8-11 weeks after induction), the population of newly formed hepatocytes is characterized by the absence of morphologically damaged cells and of cells with micronuclei, a low incidence of binuclear cells (1-3%), and a high value of proliferative pool (83-96%).
Faktor
V M
VM
Eliseeva
N A
NA
Tamakhina
A Ia
AIa
D000477:Alkylating Agents / Q000494:pharmacology*; D000818:Animals; D001345:Autoradiography; D001388:Aziridines / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured / Q000187:drug effects / Q000648:ultrastructure; D008099:Liver / Q000187:drug effects* / Q000648:ultrastructure; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects*; D011123:Polyploidy; D013997:Time Factors
D000477:Alkylating Agents; D001388:Aziridines; C007526:dipin
Vliianie alkiliruiushchego kantserogena dipina na proliferatsiiu, uroven' razvitiia poliploidii i obrazovanie mikroiader v populiatsii iskhodnykh i vnov' obrazovannykh gepatotsitov.