PATHOBIOLOGICAL EFFECTS OF ACETALDEHYDE IN CULTURED HUMAN EPITHELIAL-CELLS AND FIBROBLASTS

The ability of acetaldehyde, a respiratory carcinogen present in tobac co smoke and automotive emissions, to affect cell viability, thiol sta tus and intracellular Ca2+ levels and to cause DNA damage and mutation s has been studied using cultured human cells. Within a concentration range of 3-100 mM, a Ih exposure to acetaldehyde decreases colony surv ival and inhibits uptake of the vital dye neutral red in bronchial epi thelial cells. Acetaldehyde also causes both DNA interstrand cross-lin ks and DNA protein cross-links whereas no DNA single strand breaks are detected. The cellular content of glutathione is also decreased by ac etaldehyde, albeit, without concomitant changes in the glutathione red ox 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 O-6-methylguanine-DNA methyltra nsferase. Finally, a 5 h exposure to acetaldehyde causes significant l evels of 6-thioguanine resistance mutations in an established mutagene sis model involving skin fibroblasts. The results indicate that mM con centrations of acetaldehyde cause a wide range of cytopathic effects a ssociated with multistep carcinogenesis. The fact that acetaldehyde, i n relation to its cytotoxicity, causes comparatively higher genotoxici ty and inhibits DNA repair more readily than other major aldehydes in tobacco smoke and automotive emissions is discussed.