Glutathione S-transferase isoenzymes and glutathione peroxidase activity in normal and tumour samples from human lung

An increasing body of evidence suggests that glutatwhione-dependent enzymes are an important factor in determining the sensitivity of tumours to cytotoxic drugs. Ten randomized normal and tumour samples from individuals with lung cancer were analysed for ghitathione S-transferase isoenzyme (GST) content and ghitathione peroxidase (Gpx) activity. The normal tissue samples exhibited a 5.1- and 7.0-fold variation in GST and Gpx activity respectively. High levels of the π class, acidic Yf, GST subunit were found in all the samples, with little variation between individuals. The concentration of α and μ class subunits was 5- to 10-fold lower and were subject to significant individual variability. The μ class subunit identified had a faster mobility on SDS-PAGE than the hepatic GST μ standard and did not appear subject to the genetic polymorphism associated with certain members of this gene family. This suggests the presence of a novel pulmonary protein which may correspond to the rat Yn Yn protein. The normal to tumour ratio for GST activity varied significantly between the samples and tended to follow the relative expression of the μ class subunit, and to a lesser extent the α class GST subunit. The π subunit was present in the normal and tumour cells in very similar concentration. The expression of the μ class GST appeared to follow the differences in GST enzymic activity and although the numbers were small appeared to segregate according to tumour type. Gpx activity was also elevated in certain tumours. Of particular interest were the two adenocarcinomas which had a 20- to 30-fold higher tumour Gpx activity.