| Summary: | 碩士 === 國防醫學院 === 牙醫科學研究所 === 98 === Acetaldehyde, a cytotoxic and carcinogenic agent, is the immediate metabolite of ethanol metabolism. Recent epidemiological studies indicate that acetaldehyde may play an important role in alcohol-induced carcinogenesis in upper digestive tract. Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) are the principal enzymes responsible for metabolism of ethanol in humans. Both enzymes exhibit multiple isozymes with tissue specificity and ethnic distinct allozymes. The purpose of this thesis is to investigate expression pattern and cellular localization of ADH and ALDH families in human submandibular gland. The isozymes of ADH/ALDH were separated by isoelectric focusing in polyacrylamide gels and identified by staining for enzymes activities. Immunohistochemistry was performed using purified class-specifc rabbit polyclonal antibodies against the respective ADH/ALDH isozymes. Histochemistry was carried out staining for ADH/ALDH isozyme activities. ADH1B and ALDH1A1 were the major isozymes detected, ALDH2 and ALDH3A1 also detected to a lesser intensity in human submandibular gland by isoelectric focusing. Immunohistochemistry showed that ADH1, ALDH2 and ALDH3A1 were predominantly expressed in the cells of the striated and excretory ducts, and serous acinus. ADH3 and ALDH1A1 were also detected in these cell types, and to a lesser extent in the mucous acinus. Histochemistry showed a similar cellular localization of the activities of ADH1, ALDH1A1/2 and ALDH3A1. Moderate expression of ADH1B and low expression of ALDH1A1 and ALDH2 in human submandibular gland suggest a potential accumulation of acetaldehyde in salivary gland and in the saliva during alcohol consumption, which may contribute to alcohol-induced tissue injury. High-activity ADH1B2 and deficiency in ALDH2 may enhance vulnerability to alcohol-induced salivary gland damage and carcinogenesis in upper digestive tract in East Asians. This influence for ethnic distinction needs further molecular epidemiological studies.
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