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Cell Biology International (2010) 34, 1273–1282 (Printed in Great Britain)
Review article
Effect of formaldehyde on cell proliferation and death
Béla Szende* and Ernő Tyihák†1
*1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary, and †Institute of Plant Protection of the Hungarian Academy of Sciences, Budapest, Hungary

Formaldehyde (HCHO) may reach living organisms as an exogenous agent or produced within cells. The so-called formaldehydogenic compounds like S-adenosyl-L-methionine, N-hydroxymethyl-L-arginine, 1′-methyl ascorbigen, methanol, E-N-trimethyl lysine and methylamine are special exogenous sources of HCHO. Endogenous HCHO can be formed from hydroxymethyl groups during enzymatic methylation and demethylation processes. HCHO, as a highly reactive compound, is considered to be involved in the induction of apoptosis, consequently in the pathogenesis of atherosclerosis and neurodegenerative processes. The biological action of HCHO is dose-dependent. In vitro studies on tumour cell and endothelial cell cultures showed that HCHO in the concentration of 10.0 mM caused necrotic cell death, 1.0 mM resulted in enhanced apoptosis and reduced mitotic activity, while 0.5 and 0.1 mM enhanced cell proliferation and reduced apoptotic activity. Among formaldehydogenic compounds N-hydroxymethyl-L-arginine, 1'-methyl ascorbigen and the HCHO donor resveratrol may be considered as potential inhibitors of cell proliferation. Endogenous HCHO in plants apparently play a role in regulation of apoptosis and cell proliferation. The genotoxic and carcinogentic effects of HCHO is due to production of DNA–protein cross-links. Low doses of HCHO, reducing apoptotic activity may also accumulate cells with such cross-links. Experimental data point to the possible therapeutic use of methylated lysine residues and methylated arginine residues in the case of neoplasms.

Key words: apoptosis, cell proliferation, formaldehyde, formaldehydogenic compound

Abbreviations: HCHO, formaldehyde, MA, methylamine, SAM, S-adenosyl-l-methionine, SMC, smooth muscle cells, SSAO, semicarbazide-sensitive amine oxidase, TML, trimethyl lysine

1To whom correspondence should be addressed (email

Part of a series marking the 70th birthday of the Cell Biology International Editor-in-Chief Denys Wheatley

Received 12 July 2010; accepted 7 October 2010

Published online 11 November 2010, doi:10.1042/CBI20100532

© The Author(s) Journal compilation © 2010 Portland Press Limited

ISSN Print: 1065-6995
ISSN Electronic: 1095-8355
Published by Portland Press Limited on behalf of the International Federation for Cell Biology (IFCB)