Marselos M, Vasiliou V
Department of Pharmacology, Medical School, University of Ioannina, Greece.
Chem Biol Interact. 1991;79(1):79-89. doi: 10.1016/0009-2797(91)90054-b.
The cytosolic activity of aldehyde dehydrogenase (ALDH) was studied in the rat liver, after acute administration of various carcinogenic and chemically related compounds. Male Wistar rats were treated with 27 different chemicals, including polycyclic aromatic hydrocarbons, aromatic amines, nitrosamines, azo dyes, as well as with some known direct-acting carcinogens. The cytosolic ALDH activity of the liver was determined either with propionaldehyde and NAD (P/NAD), or with benzaldehyde and NADP (B/NADP). The activity of ALDH remained unaffected after treatment with 1-naphthylamine, nitrosamines and also with the direct-acting chemical carcinogens tested. On the contrary, polycyclic aromatic hydrocarbons, polychlorinated biphenyls (Arochlor 1254) and 2-naphthylamine produced a remarkable increase of ALDH. In general, the response to the effectors was disproportionate between the two types of enzyme activity, being much in favour for the B/NADP activity. This fact resulted to an inversion of the ratio B/NADP vs. P/NAD, which under constitutive conditions is lower than 1. In this respect, the most potent compounds were found to be polychlorinated biphenyls, 3-methylcholanthrene, benzo(a)pyrene and 1,2,5,6-dibenzoanthracene. Our results suggest that the B/NADP activity of the soluble ALDH is greatly induced after treatment with compounds possessing aromatic ring(s) in their molecule. It is not known, if this response of the hepatocytes is related with the process of chemical carcinogenesis.
在急性给予各种致癌及化学相关化合物后,对大鼠肝脏中醛脱氢酶(ALDH)的胞质活性进行了研究。用27种不同的化学物质处理雄性Wistar大鼠,这些化学物质包括多环芳烃、芳香胺、亚硝胺、偶氮染料以及一些已知的直接作用致癌物。肝脏的胞质ALDH活性通过丙醛和NAD(P/NAD)或苯甲醛和NADP(B/NADP)来测定。用1-萘胺、亚硝胺以及所测试的直接作用化学致癌物处理后,ALDH活性未受影响。相反,多环芳烃、多氯联苯(Arochlor 1254)和2-萘胺使ALDH显著增加。一般来说,两种类型的酶活性对效应物的反应不成比例,更有利于B/NADP活性。这一事实导致B/NADP与P/NAD的比值发生反转,在组成条件下该比值低于1。在这方面,发现最有效的化合物是多氯联苯、3-甲基胆蒽、苯并(a)芘和1,2,5,6-二苯并蒽。我们的结果表明,用分子中含有芳环的化合物处理后,可溶性ALDH的B/NADP活性会被极大地诱导。尚不清楚肝细胞的这种反应是否与化学致癌过程有关。