Effect of formaldehyde on cell proliferation and death.
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.
1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary.
Béla
B
Szende
Erno
E
Tyihák
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001120:Arginine / Q000378:metabolism / Q000494:pharmacology; D002273:Carcinogens / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology / Q000600:supply & distribution; D016923:Cell Death / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005557:Formaldehyde / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology* / Q000600:supply & distribution; D006801:Humans; D008954:Models, Biological
D002273:Carcinogens; D005557:Formaldehyde; D001120:Arginine