Elevated activity of beta-hexosaminidase and sulfhydryl modification in the B-variant of human lung cancer.

Activities of beta-hexosaminidase A and beta-hexosaminidase B (Hex B) were measured both in human lung carcinoma and the adjacent normal tissues of 47 patients. The specific activity of total beta-hexosaminidase in the tumors was considerably higher than in the adjacent normal tissues, irrespective of histological types. In isoelectric focusing experiments, Hex B purified from normal lung exhibited a single peak with an isoelectric point (pI) of 7.9, while Hex B purified from adenocarcinoma contained two forms with pI 7.6 and 7.9. With respect to heat stability, Hex B from the normal lung was very stable at 52 degrees, while the tumor Hex B (mixture of pI 7.6 and 7.9 forms) was unstable. After treatment of the tumor enzyme with dithiothreitol, heat stability was restored. When the tumor pI 7.6 form was treated with dithiothreitol and subjected to polyacrylamide gel electrophoresis, the enzyme converted to a pI 7.9 form similar to that of the normal lung. Determination of the sulfhydryl group of the tumor pI 7.6 form under nondenaturing conditions showed that the enzyme had some easily reducible disulfide bonds on its surface. These findings indicate that the formation of mixed disulfide bonds in the tumor Hex B increases the net negative charge and results in the appearance of a heat-labile form.