Cytotoxicity, thiol depletion and inhibition of O6-methylguanine-DNA methyltransferase by various aldehydes in cultured human bronchial fibroblasts

Lipid peroxidation aldehydes of the 4-hydroxy-, ß-unsaturatedtype, as well as the tobacco-smoke related , ß-unsaturatedaldehyde, acrolein, were highly cytotoxic and decreased theintracellular thiol content in cultured human bronchial fibroblastsafter treatment with micromolar concentrations. In comparison,formaldehyde and acetaldehyde were less toxic and 100- to 300-foldhigher doses were required to affect cell survival or thiollevels. The unsaturated aldehydes also markedly inhibited theDNA repair enzyme O⁶-methylguanine-DNA methyltransferase knownto have a cysteine residue in its active site, but had no effecton the activity of uracil-DNA glycosylase. Our results indicatethat reactive aldehydes of either exogenous or endogenous originhave direct cytotoxic effects and may also make cells more susceptibleto other toxic chemicals due to an impairment in cellular defensemechanisms, e.g., DNA repair and detoxification by systems requiringglutathione.