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Mechanisms of Acetaldehyde‐Mediated Growth Inhibition: Delayed Cell Cycle Progression and Induction of Apoptosis
Author(s) -
Zimmerman Barbara T.,
Crawford Garrett D.,
Dahl Rolf,
Simon Francis R.,
Mapoles John E.
Publication year - 1995
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.1530-0277.1995.tb01527.x
Subject(s) - acetaldehyde , cell cycle , apoptosis , cell growth , alcohol dehydrogenase , programmed cell death , biology , microbiology and biotechnology , cell division , aldehyde dehydrogenase , fragmentation (computing) , cell cycle checkpoint , cell culture , ethanol , cell , dna fragmentation , cyclin dependent kinase 1 , chemistry , biochemistry , genetics , enzyme , ecology
Chronic ethanol exposure has been associated with pleiotropic effects on cellular function in vivo and in vitro, including inhibition of growth. To date, it has been difficult to dissociate the primary effects of ethanol from the effects of ethanol metabolism, generation of acetaldehyde, and reducing equivalents. We have previously described the development of a Chinese hamster ovary cell line, A‐10, which expresses a transfected murine‐liver alcohol dehydrogenase. Cultures of these cells accumulate acetaldehyde due to the low level of aldehyde dehydrogenase. One noticeable effect of chronic acetaldehyde exposure, but not ethanol exposure, is the inhibition of cell growth. This study focuses on the mechanisms that underlie this growth inhibition. Our studies with the A‐10 cell on the rates of [ 3 H]thymidine incorporation and flow cytometry of asynchronous cultures indicated that acetaldehyde did not lead to arrest of the cell cycle in the G 1 phase as has been found in other models of ethanol exposure. Rather, we observed a generalized delay in cell cycle progression. However, the slower cell cycle did not account exclusively for the slower rates of cell accumulation. Chronic exposure to acetaldehyde also increased the rate of cell death. The increased rate of cell death was both cumulative and dose‐dependent. The dead cells accumulated in the medium and were apoptotic. Apoptosis was confirmed using morphological criteria and quantitation of DNA fragmentation. These data lend additional support to the idea that chronic acetaldehyde exposure can affect the mechanisms that regulate cell division and the apoptotic program.