Alterations in growth rate and cell cycle kinetics of rat liver tumor cells cultured in ethanol-containing medium. In vitro model of proliferative restriction in response to ethanol exposure |
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| Authors: | P J Higgins E Borenfreund |
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| Affiliation: | 3. Laboratory Animal Research Center, Rockefeller University, New York, NY 10021, U.S.A.;1. Division of Nephrology and Hypertension, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL, USA;2. Division of Nephrology and Hypertension, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA;3. Center for Translational Metabolism and Health, Institute for Public Health and Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA;4. Department of Pediatrics, University of Miami Miller School of Medicine, Miami, FL, USA;5. Department of Medicine, Duke University School of Medicine, Durham, NC, USA;6. Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC, USA;7. Section of Nephrology, Department of Medicine, University of Illinois, Chicago, IL, USA;8. Section of Nephrology and Hypertension, Department of Medicine, Tulane School of Medicine, New Orleans, LA, USA;9. Selzman Institute for Kidney Health, Section of Nephrology, Department of Medicine, Baylor College of Medicine, Houston, TX, USA;10. Section of Nephrology, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX, USA;11. Division of Nephrology and Hypertension, Department of Medicine, University Hospitals Case Medical Center, Case Western Reserve University School of Medicine, Cleveland, OH, USA;12. Joslin Diabetes Center, Beth Israel Deaconess Hospital, Harvard Medical School, Boston, MA, USA;13. Division of Nephrology, Department of Medicine, University of Michigan, Ann Arbor, MI, USA;14. University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA;15. Division of Renal Diseases and Hypertension, George Washington University, Washington, DC, USA;1. Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan;2. Department of Pharmacology, Kagawa University School of Medicine, Kagawa, Japan;3. Department of Molecular Biology, Yokohama City University Graduate School of Medicine, Yokohama, Japan;4. Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan;1. Departamento de Bacteriología y Virología, Instituto de Higiene, Facultad de Medicina, Universidad de la República, Alfredo Navarro 3051, CP: 11600 Montevideo, Uruguay;2. Laboratorio Central del Centro Hospitalario Pereira Rossell, Ministerio de Salud Pública, Montevideo, Uruguay;3. Departamento de Pediatría, Centro Hospitalario Pereira Rossell, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay;1. Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal 576104, Karnataka, India;2. Department of Pharmaceutical Chemistry, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal 576104, Karnataka, India;1. 1st Cardiology Clinic, University of Athens, Athens, Greece;2. Department of Nutrition-Dietetics, School of Health and Education, Harokopio University, Athens, Greece;1. Institute of Industrial Science, The University of Tokyo, Tokyo 153-8505, Japan;2. Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo 153-8505, Japan;3. Department of Chemistry and Biotechnology, The University of Tokyo, Tokyo 153-8505, Japan |
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| Abstract: | ![]()
Mechanisms related to the growth suppressive effect of acute ethanol exposure on liver cells were investigated using an established line of ethanol-sensitive rat hepatic tumor cells (32IIIA) and recently developed cytochemical methods for analysis of hepatocyte cell cycle kinetics. Exposure of exponentially growing 32IIIA cells to ethyl alcohol (range 10-100 mM in the growth medium) for a period of 3 days resulted in concentration-dependent decreases (4-25%) in final population density and increases (18-35%) in mean population doubling time compared to untreated cells. Viability was unaffected by ethanol exposure in the concentrations indicated and for the duration period utilized, approximating 94% under all experimental conditions. Multiparametric flow cytometric analysis revealed significant ethanol-associated differences in specific growth parameters and growth state compartments of 32IIIA hepatic tumor cell populations. Most prominent was an ethanol-associated and concentration-dependent (a) increase in the fraction of cells in the G1 phase of the cell cycle, (b) increase in the coefficient of variation in the G1 DNA content measurement, and (c) accumulation (in the G1 phase) of cells with a very low mean RNA content. Increases in each of these cytochemically-defined parameters reflected increasing levels of ethanol in the growth medium. This study indicates that the effects of ethanol on cultured cells of hepatic origin are quite complex. It is concluded that the inhibition of proliferation observed during acute ethanol exposure of liver-derived 32IIIA cells in vitro is due to an accumulation of cells in the G1 compartment. |
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