Abstract:
:Lipid peroxidation aldehydes of the 4-hydroxy-alpha, beta-unsaturated type, as well as the tobacco-smoke related alpha, beta-unsaturated aldehyde, acrolein, were highly cytotoxic and decreased the intracellular thiol content in cultured human bronchial fibroblasts after treatment with micromolar concentrations. In comparison, formaldehyde and acetaldehyde were less toxic and 100- to 300-fold higher doses were required to affect cell survival or thiol levels. The unsaturated aldehydes also markedly inhibited the DNA repair enzyme O6-methylguanine-DNA methyltransferase known to have a cysteine residue in its active site, but had no effect on the activity of uracil-DNA glycosylase. Our results indicate that reactive aldehydes of either exogenous or endogenous origin have direct cytotoxic effects and may also make cells more susceptible to other toxic chemicals due to an impairment in cellular defense mechanisms, e.g., DNA repair and detoxification by systems requiring glutathione.
journal_name
Carcinogenesisjournal_title
Carcinogenesisauthors
Krokan H,Grafstrom RC,Sundqvist K,Esterbauer H,Harris CCdoi
10.1093/carcin/6.12.1755subject
Has Abstractpub_date
1985-12-01 00:00:00pages
1755-9issue
12eissn
0143-3334issn
1460-2180journal_volume
6pub_type
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