Cell cycle phase-specific perturbation of hepatic tumor cell growth kinetics during short-term in vitro exposure to ethanol.
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 less than 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 G1 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 G1 phase cells within a culture. Lower overall G1 cellular RNA content typified all ethanol-treated 32IIIA tumor cell populations. The fraction of G1 cells in the immediate pre-DNA-synthetic (G1B) compartment was markedly reduced (by 41-80%) during the period of ethanol exposure as were the percentages of S and G2+M phase cells which derive kinetically from cells in G1B. This reduction in the proportion of cells with normal G1B RNA levels was not reflected solely in the complement of very low RNA content "G1E-type" cells generated during the course of ethanol treatment. Net accumulations (of 19 and 34%) of cells residing in the G1A 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 G1 phase of the cell division cycle.(ABSTRACT TRUNCATED AT 250 WORDS)
Higgins
P J
PJ
Laboratory of Cell and Molecular Biology, Veterans Administration Medical Center, Albany, New York 12208.
D000818:Animals; D002453:Cell Cycle / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D000431:Ethanol / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology*; D008114:Liver Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology*; D012334:RNA, Neoplasm / Q000096:biosynthesis; D051381:Rats
D012334:RNA, Neoplasm; D000431:Ethanol