Carcinogenesis, Vol 19, 2031-2036, Copyright © 1998 by Oxford University Press
T Koivisto and M Salaspuro
Studies with experimental animals indicate that acetaldehyde, the first
metabolite of ethanol that is microbially formed in the colonic lumen, may
play a role in ethanol-associated colorectal co-carcinogenesis. Although
intracoIonic acetaldehyde concentrations are highest during the metabolism
of exogenous ethanol, some individuals may also possess marked amounts of
endogenous acetaldehyde. Since no information is available concerning the
possible effects of acetaldehyde on human colonic epithelial cells, this
study was aimed to assess whether this compound, either alone or in
combination with ethanol, affects such properties of human neoplastic
colonocytes that are considered relevant with regard to cancer development.
Human colon adenocarcinoma cell line Caco-2 was used as a model of
transformed colonocytes, and effects of acetaldehyde and/or ethanol on the
proliferation and differentiation of these cells as well as on their
adhesion to collagens I and IV, the most important extracellular matrix
proteins in the colon, were studied. The results of this study show that
acetaldehyde markedly affects the phenotype of Caco-2 cells without having
direct cytotoxic effects. Like many carcinogens, it was found to have a
dual effect on cell proliferation rate, acute exposure being inhibitory and
chronic exposure stimulating. Acetaldehyde also considerably decreased both
sucrase activity and nuclear content of protein kinase A catalytic subunit
in Caco-2 cells, which indicate that the differentiation of the cells was
disturbed. Moreover, the adhesion of Caco-2 cells to collagens I and IV was
dose-dependently reduced by acetaldehyde treatment. All these changes, i.e.
enhanced cell proliferation rate (by chronic treatment), decreased
differentiation, and reduced adhesion to extracellular matrix proteins,
would in vivo predict more aggressive and invasive tumour behaviour. The
possibility that colonic intraluminal acetaldehyde, either ethanol-derived
or endogenous, might enhance the development of colorectal tumours should
therefore be considered.
ARTICLES
Acetaldehyde alters proliferation, differentiation and adhesion properties of human colon adenocarcinoma cell line Caco-2
Research Unit of Alcohol Diseases, Helsinki University Central Hospital, Finland.
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