Pathobiological effects of acetaldehyde in cultured human epithelial cells and fibroblasts.
The ability of acetaldehyde, a respiratory carcinogen present in tobacco smoke and automotive emissions, to affect cell viability, thiol status and intracellular Ca2+ levels and to cause DNA damage and mutations has been studied using cultured human cells. Within a concentration range of 3-100 mM, a 1 h exposure to acetaldehyde decreases colony survival and inhibits uptake of the vital dye neutral red in bronchial epithelial cells. Acetaldehyde also causes both DNA interstrand cross-links and DNA protein cross-links whereas no DNA single strand breaks are detected. The cellular content of glutathione is also decreased by acetaldehyde, albeit, without concomitant changes in the glutathione redox status or in the content of protein thiols. Transient or sustained increases in cytosolic Ca2+ occur within minutes following exposure of cells to acetaldehyde. Moreover, acetaldehyde significantly decreases the activity of the DNA repair enzyme O6-methylguanine-DNA methyltransferase. Finally, a 5 h exposure to acetaldehyde causes significant levels of 6-thioguanine resistance mutations in an established mutagenesis model involving skin fibroblasts. The results indicate that mM concentrations of acetaldehyde cause a wide range of cytopathic effects associated with multistep carcinogenesis. The fact that acetaldehyde, in relation to its cytotoxicity, causes comparatively higher genotoxicity and inhibits DNA repair more readily than other major aldehydes in tobacco smoke and automotive emissions is discussed.
Grafström
R C
RC
Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Dypbukt
J M
JM
Sundqvist
K
K
Atzori
L
L
Nielsen
I
I
Curren
R D
RD
Harris
C C
CC
D000079:Acetaldehyde / Q000633:toxicity*; D000171:Acrolein / Q000633:toxicity; D002118:Calcium / Q000378:metabolism; D002470:Cell Survival; D002478:Cells, Cultured; D004247:DNA / Q000187:drug effects; D004249:DNA Damage; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D005557:Formaldehyde / Q000633:toxicity; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008780:Methyltransferases / Q000378:metabolism; D008954:Models, Biological; D016296:Mutagenesis; D009499:Neutral Red / Q000493:pharmacokinetics; D019853:O(6)-Methylguanine-DNA Methyltransferase; D010084:Oxidation-Reduction; D011506:Proteins / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000378:metabolism
D011506:Proteins; D013438:Sulfhydryl Compounds; D005557:Formaldehyde; D009499:Neutral Red; D000171:Acrolein; D004247:DNA; D008780:Methyltransferases; D019853:O(6)-Methylguanine-DNA Methyltransferase; D005978:Glutathione; D000079:Acetaldehyde; D002118:Calcium