Histochemical localization of primary and secondary alcohol dehydrogenases in whole-body, freeze-dried sections of mice.
Whole-body sagittal sections of frozen, C57BL/6J, adult, male mice were used for the localization of primary and secondary alcohol dehydrogenases in most tissues of the body. The reduction of Nitro BT with NAD+ as coenzyme, as described originally by Hardonk (1965), was utilized for the generation of coloured final reaction deposits. Ethanol was used as a substrate for primary alcohol dehydrogenase; 2-propanol, alpha-methylbenzyl alcohol and 2-butanol were used as substrates for secondary alcohol dehydrogenase. Liver and bronchial epithelium showed the highest activities for both enzymes; oesophageal and upper gastric epithelium showed a high activity of primary alcohol dehydrogenase. Pyrazole, indazole and imidazole inhibited primary, but not secondary, alcohol dehydrogenase. Dimethylsulphoxide and menthol slightly inhibited both enzymes. Oleic acid, sulphydryl agents, p-chloromercuribenzoate, and copper sulphate also inhibited both enzymes. Slight inhibition of secondary dehydrogenase was observed on co-administration of several alcohols. As expected, N-nitrosonornicotine did not function as a substrate for alcohol dehydrogenases. When this compound was present in the histochemical incubation media, no activity was seen at any of the usual sites of these enzymes. The distribution of the alcohol dehydrogenase activities found in this study correlates with the distribution of radioactivity in oesophagus, bronchi and liver after administration of [14C]nitrosonornicotine. This suggests that the alcohol dehydrogenases may be involved in the metabolism of hydroxylated nitrosonornicotine, a metabolite of the most abundant known carcinogen in cigarette smoke.
D000429:Alcohol Oxidoreductases / Q000378:metabolism*; D000818:Animals; D001980:Bronchi / Q000201:enzymology; D006651:Histocytochemistry; D008099:Liver / Q000201:enzymology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009602:Nitrosamines; D013379:Substrate Specificity; D014018:Tissue Distribution
D009602:Nitrosamines; D000429:Alcohol Oxidoreductases; C008655:N'-nitrosonornicotine