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Cell Cycle Phase‐Specific Perturbation of Hepatic Tumor Cell Growth Kinetics during Short‐Term in Vitro Exposure to Ethanol
Author(s) -
Higgins Paul J.
Publication year - 1987
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.1987.tb00172.x
Subject(s) - ethanol , cell cycle , population , cell growth , in vitro , cell , hepatic stellate cell , cell culture , dna synthesis , doubling time , biology , chemistry , flow cytometry , biochemistry , microbiology and biotechnology , andrology , endocrinology , medicine , genetics , environmental health
Cell cycle events associated with the growth suppressive effects of short‐term ethanol exposure on liver cells were investigated using flow cytometric methods to analyze the proliferative kinetics of ethanol‐sensitive 32IIIA rat hepatic tumor cells. A 3‐day exposure of exponentially growing 32IIIA cells to growth medium containing 100 mM ethyl alcohol decreased final population density (to <70% of control values) although viability was unaffected, approximating 94% under all experimental conditions. Comparative flow cytometric analysis of control and ethanol‐treated populations revealed significant ethanol‐associated alterations in the substate composition of G 1 phase hepatic tumor cells. An ethanol‐induced 30% increase in mean population doubling time was reflected in an approximately 22% increase in the proportion of G 1 phase cells within a culture. Lower overall G 1 cellular RNA content typified all ethanol‐treated 32IIIA tumor cell populations. The fraction of G 1 cells in the immediate pre‐DNA‐synthetic (G 18 ) compartment was markedly reduced (by 41–80%) during the period of ethanol exposure as were the percentages of S and G 2 +M phase cells which derive kinetically from cells in G 18 . This reduction in the proportion of cells with normal G 18 RNA levels was not reflected solely in the complement of very low RNA content “G 1E ‐type” cells generated during the course of ethanol treatment. Net accumulations (of 19 and 34%) of cells residing in the G 1A substate were consistent additional concomitants of ethanol treatment. Short‐term ethanol exposure in the 32IIIA hepatic tumor cell system clearly impairs normal progression of such cells through the G 1 phase of the cell division cycle. This inhibition appears to be due specifically to interference with orderly transition from G 1A into the immediate pre‐DNA‐synthetic G 1B substate resulting in a net accumulation of cells in the G 1A subcompartment.