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(American Journal of Pathology. 2000;157:1745-1755.)
© 2000 American Society for Investigative Pathology

Regular Articles

Expression of Alcohol Dehydrogenase 3 in Tissue and Cultured Cells from Human Oral Mucosa

Jesper J. Hedberg*, Jan-Olov Höög*, Jan A. Nilsson{dagger}, Zheng Xi{dagger}, Åsa Elfwing{dagger} and Roland C. Grafström{dagger}

From the Department of Medical Biochemistry and Biophysics*
and the Institute of Environmental Medicine,{dagger}
Karolinska Institutet, Stockholm, Sweden

Because formaldehyde exposure has been shown to induce pathological changes in human oral mucosa, eg, micronuclei, the potential enzymatic defense by alcohol dehydrogenase 3 (ADH3)/glutathione-dependent formaldehyde dehydrogenase was characterized in oral tissue specimens and cell lines using RNA hybridization and immunological methods as well as enzyme activity measurements. ADH3 mRNA was expressed in basal and parabasal cell layers of oral epithelium, whereas the protein was detected throughout the cell layers. ADH3 mRNA and protein were further detected in homogenates of oral tissue and various oral cell cultures, including, normal, SV40T antigen-immortalized, and tumor keratinocyte lines. Inhibition of the growth of normal keratinocytes by maintenance at confluency significantly decreased the amount of ADH3 mRNA, a transcript with a determined half-life of 7 hours. In contrast, decay of ADH3 protein was not observed throughout a 4-day period in normal keratinocytes. In samples from both tissue and cells, the ADH3 protein content correlated to oxidizing activity for the ADH3-specific substrate S-hydroxymethylglutathione. The composite analyses associates ADH3 mRNA primarily to proliferative keratinocytes where it exhibits a comparatively short half-life. In contrast, the ADH3 protein is extremely stable, and consequently is retained during the keratinocyte life span in oral mucosa. Finally, substantial capacity for formaldehyde detoxification is shown from quantitative assessments of alcohol- and aldehyde-oxidizing activities including Km determinations, indicating that ADH3 is the major enzyme involved in formaldehyde oxidation in oral mucosa.




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