OVER-EXPRESSION OF GLUTATHIONE S-TRANSFERASES, DT-DIAPHORASE AND AN APPARENTLY TUMOR-SPECIFIC CYTOSOLIC CLASS-3 ALDEHYDE DEHYDROGENASE BY WARTHIN TUMORS AND MUCOEPIDERMOID CARCINOMAS OF THE HUMAN PAROTID-GLAND

Cytosolic class-3 aldehyde dehydrogenase (ALDH-3) may help to protect organisms from certain environmental aldehydes by catalysing their det oxification. Consistent with this notion are the reports that relative ly high levels of this enzyme are present in tissues, e.g. stomach muc osa and lung, that are so-called ports of entry for such agents. Furth er, it is found in human saliva. The present investigation revealed th at small amounts of this enzyme are also present in human salivary gla nds; mean values for ALDH-3 activities (NADP-dependent enzyme-catalyse d oxidation of benzaldehyde) in cytosolic fractions prepared from subm andibular and parotid glands were 52 (range: 29-92) and 44 (range: 13- 73) mIU/g tissue, respectively. Essentially identical or slightly lowe r levels of this enzyme activity were found in pleomorphic adeno-mas, an undifferentiated carcinoma, and an adenocystic carcinomas, of the p arotid gland. On the other hand, Warthin tumours, and mucoepidermoid c arcinomas of the parotid gland exhibited relatively elevated levels of ALDH-3 activity; mean values were 1200 (range: 780-1880) and 810 (ran ge: 580-1200) mIU/g tissue, respectively. The ALDH-3 found in normal s alivary glands was, as judged by physical, immunological and kinetic c riteria, identical to human stomach mucosa ALDH-3 whereas the ALDH-3 p resent in Warthin tumours, and mucoepidermoid carcinomas, of the parot id gland appeared to be a subtle variant thereof. Qualitatively parall eling the relatively elevated ALDH-3 levels in mucoepidermoid carcinom as and Warthin tumours were relatively elevated levels of glutathione S-transferase (alpha and pi) and DT-diaphorase. As was the case with A LDH-3 levels, glutathione S-transferase (cc and pi) and DT-diaphorase levels were not elevated in pleomorphic adenomas. Glutathione S-transf erase mu was not detected in the two normal parotid gland samples, or in the single pleomorphic adenoma sample, tested. It was found in the single mucoepidermoid carcinoma sample, and in one of the two Warthin tumour samples tested. Cellular levels of ALDH-3, glutathione S-transf erases and/or DT-diaphorase could be useful criteria when the decision to be made is whether a salivary gland tumour is a mucoepidermoid car cinoma. ALDH-3 and glutathione S-transferases are known to catalyse th e detoxification of two agents that are used to treat salivary gland t umours, viz. cyclophosphamide and cisplatin, respectively. Thus, eleva ted levels of these enzymes in the mucoepidermoid carcinomas must acco unt for, or at least contribute to, the relative ineffectiveness of th ese agents when used to treat this tumour. Copyright (C) 1996 Elsevier Science Ltd.