Falany C N, Wilborn T W
Department of Pharmacology, University of Alabama at Birmingham 35294.
Adv Pharmacol. 1994;27:301-29. doi: 10.1016/s1054-3589(08)61037-6.
Numerous studies have indicated that two classes of cytosolic STs are involved in the bioactivation of procarcinogens and drugs to reactive electrophiles, especially in rodent tissues. These two classes of STs are the hydroxysteroid STs, which are involved in the conjugation of hydroxymethyl PAHs, and the phenol STs involved in the sulfation of alkenylbenzenes and N-hydroxyarylamines. Purification studies of rat liver STs have clearly indicated that specific isoforms of hydroxysteroid and phenol STs are capable of sulfating procarcinogens in vitro. Rat liver STa and BAST I are structurally similar hydroxysteroid STs, which have been shown to sulfate and bioactive HMBA. Molecular cloning studies of the rat hydroxysteroid STs indicate that these enzymes are probably part of a family of closely related genes. The single human hydroxysteroid ST that has been characterized is very similar to the rat enzymes, but its role in the bioactivation of hydroxymethyl PAHs has not been established. Phenol STs have been demonstrated to have an important role in the bioactivation of alkenylbenzenes and N-hydroxyarylamines. Purification of rat phenol STs has identified several different forms, but only some appear to be involved in bioactivation of procarcinogens. Four isoforms (HAST I and II, AST III and IV) are apparently responsible for the majority of N-hydroxyarylamine sulfation. The relationship between these enzymes has not been established but they may represent similar enzymes. Different isoforms of rat phenol ST are also involved in the bioactivation of procarcinogens and drugs. However, the role of these phenol STs, PST-1, Mx-ST, and paracetamol ST, in carcinogenesis requires further study. In human tissues, only two phenol STs, P-PST and M-PST, have been identified. The role of these enzymes or unidentified STs in the sulfation of N-hydroxyarylamine procarcinogens has not yet been established. Initial reports of the molecular cloning and expression of the rat and human phenol ST genes will provide a valuable mechanism for the characterization of roles of the individual enzymes in bioactivation.
众多研究表明，两类胞质磺基转移酶（STs）参与了前致癌物和药物向反应性亲电试剂的生物活化过程，尤其是在啮齿动物组织中。这两类STs分别是羟基类固醇STs，其参与羟甲基多环芳烃的结合反应；以及酚类STs，其参与烯基苯和N-羟基芳胺的硫酸化反应。对大鼠肝脏STs的纯化研究清楚地表明，羟基类固醇和酚类STs的特定同工型能够在体外将前致癌物硫酸化。大鼠肝脏STa和BAST I是结构相似的羟基类固醇STs，已证明它们能将具有生物活性的HMBA硫酸化。对大鼠羟基类固醇STs的分子克隆研究表明，这些酶可能是一个密切相关基因家族的一部分。已鉴定出的单一人类羟基类固醇ST与大鼠酶非常相似，但其在羟甲基多环芳烃生物活化中的作用尚未确定。酚类STs已被证明在烯基苯和N-羟基芳胺的生物活化中起重要作用。对大鼠酚类STs的纯化已鉴定出几种不同形式，但只有一些似乎参与前致癌物的生物活化。四种同工型（HAST I和II、AST III和IV）显然负责大部分N-羟基芳胺的硫酸化。这些酶之间的关系尚未确定，但它们可能代表相似的酶。大鼠酚类ST的不同同工型也参与前致癌物和药物的生物活化。然而，这些酚类STs，即PST-1、Mx-ST和对乙酰氨基酚ST，在致癌作用中的作用需要进一步研究。在人体组织中，仅鉴定出两种酚类STs，即P-PST和M-PST。这些酶或未鉴定的STs在N-羟基芳胺前致癌物硫酸化中的作用尚未确定。关于大鼠和人类酚类ST基因的分子克隆和表达的初步报告将为表征各个酶在生物活化中的作用提供有价值的机制。
