Werle-Schneider G, Schwarz M, Glatt H
Department of Toxicology, University of Mainz, Germany.
Carcinogenesis. 1993 Nov;14(11):2267-70. doi: 10.1093/carcin/14.11.2267.
Rat liver cytosolic hydroxysteroid sulfotransferases form highly reactive sulfuric acid esters from some benzylic alcohols, such as 1-hydroxymethylpyrene. In this study we examined the expression of hydroxysteroid sulfotransferase a (STa) in carcinogen-induced enzyme-altered, presumably preneoplastic, rat liver foci. Female Wistar rats were given a single i.p. injection of diethylnitrosamine (0.15 mumol/g body wt) 1 day after birth to induce the liver foci. After weaning, rats were given 1-hydroxymethylpyrene or phenobarbital continuously in their diet (250 or 500 p.p.m. respectively) for a total of 120 days. Carcinogen-induced liver foci were identified by a change in the marker enzyme adenosine triphosphatase. Immunohistochemical staining of consecutive sections using an anti-STa rabbit antibody demonstrated that STa was expressed at decreased levels in most of the adenosine triphosphatase-negative liver foci. This effect was observed in both 1-hydroxymethylpyrene- and phenobarbital-treated animals. The decrease in STa content in enzyme-altered foci may lead to a selective advantage of the preneoplastic cells in the presence of agents that are able to form reactive sulfuric acid esters, such as 1-hydroxymethylpyrene. In some diethylnitrosamine/phenobarbital-treated rats, a small number of atypical foci were observed, most of them showing enhanced expression of STa and unchanged to moderately increased ATPase activity.
大鼠肝细胞溶质型羟基类固醇硫酸转移酶可由某些苄醇（如1-羟甲基芘）形成高反应性硫酸酯。在本研究中，我们检测了致癌物诱导的、推测为癌前病变的大鼠肝灶中羟基类固醇硫酸转移酶a（STa）的表达。雌性Wistar大鼠在出生后1天经腹腔注射一次二乙基亚硝胺（0.15 μmol/g体重）以诱导肝灶形成。断奶后，大鼠在其饮食中持续给予1-羟甲基芘或苯巴比妥（分别为250或500 ppm），共120天。通过标记酶三磷酸腺苷酶的变化来鉴定致癌物诱导的肝灶。使用抗STa兔抗体对连续切片进行免疫组织化学染色表明，在大多数三磷酸腺苷酶阴性的肝灶中，STa表达水平降低。在1-羟甲基芘和苯巴比妥处理的动物中均观察到这种效应。在酶改变的病灶中STa含量的降低可能会使癌前细胞在存在能够形成反应性硫酸酯的物质（如1-羟甲基芘）时具有选择性优势。在一些经二乙基亚硝胺/苯巴比妥处理的大鼠中，观察到少数非典型病灶，其中大多数显示STa表达增强且三磷酸腺苷酶活性不变至中度增加。
