Mainwaring G W, Williams S M, Foster J R, Tugwood J, Green T
Zeneca Central Toxicology Laboratory, Macclesfield, Cheshire, U.K.
Biochem J. 1996 Aug 15;318 ( Pt 1)(Pt 1):297-303. doi: 10.1042/bj3180297.
Two murine Theta-class glutathione S-transferases (GSTs), mGSTT1 and mGSTT2, have been cloned and sequenced. The murine cDNAs, together with the published sequences of the rat and human enzymes, were used to design oligonucleotide probes in order to determine the distribution of mRNA for these enzymes in the liver and lung of rat, mouse and human. The mRNA distribution was compared with that of enzyme protein determined with an antibody to rat GSTT2-2. Both the antibody and the oligonucleotide probes gave the same distribution patterns. Both enzymes were present at significantly higher concentrations in mouse tissues than in rat or human tissues. In mouse liver, both enzymes were localized in specific cell types and in nuclei. Although the distribution of GSTT2-2 in rat liver was similar to that seen in the mouse, GSTT1-1 was not localized in a specific cell type or in the nuclei of either rat or human liver. In the lungs, very high concentrations of the Theta enzymes were present in mouse-lung Clara cells and ciliated cells, with much lower levels in the Clara cells only of rat lung. Low levels of human transferase GSTT1-1 were detected in a small number of Clara cells and ciliated cells at the alveolar/ bronchiolar junction. The relative activities between species, and the cellular and sub-cellular distribution within the liver and lungs of each species, provides an explanation for the species-specificity of methylene chloride, a mouse-specific carcinogen activated by glutathione S-transferase GSTT1-1.
已克隆并测序了两种鼠源θ类谷胱甘肽S-转移酶（GSTs），即mGSTT1和mGSTT2。利用鼠源cDNA以及已发表的大鼠和人源酶序列来设计寡核苷酸探针，以确定这些酶的mRNA在大鼠、小鼠和人的肝脏及肺中的分布。将mRNA分布与用抗大鼠GSTT2-2抗体测定的酶蛋白分布进行比较。抗体和寡核苷酸探针给出了相同的分布模式。两种酶在小鼠组织中的浓度均显著高于大鼠或人组织中的浓度。在小鼠肝脏中，两种酶均定位于特定细胞类型和细胞核中。虽然大鼠肝脏中GSTT2-2的分布与小鼠相似，但GSTT1-1在大鼠或人肝脏的特定细胞类型或细胞核中均未定位。在肺中，θ类酶在小鼠肺克拉拉细胞和纤毛细胞中浓度非常高，而仅在大鼠肺的克拉拉细胞中浓度低得多。在肺泡/细支气管交界处的少数克拉拉细胞和纤毛细胞中检测到低水平的人源转移酶GSTT1-1。各物种之间的相对活性以及每个物种肝脏和肺内的细胞及亚细胞分布，为二氯甲烷的物种特异性提供了解释，二氯甲烷是一种由谷胱甘肽S-转移酶GSTT1-1激活的小鼠特异性致癌物。
