gamma-Glutamyltransferase and the inhibition of azo dye-produced neoplasia by concomitant administration of disulfiram.

The concentration and total amount of DNA in the livers of SD rats fed 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB) gradually increased and reached a maximum in developing tumors. In SD rats fed 3'-Me-DAB plus disulfiram (DSF), the concentration of DNA was higher than in controls, but it soon became stabilzed and the total amount of DNA in the liver did not differ substantially from that in rats fed DSF alone. In rats given 3'-Me-DAB, neoplastic nodules and liver carcinomas appeared after 3 months, but in those fed both compounds these formations were absent even after 6 months. The activity of gamma-glutamyltransferase (GT-ase), a marker of chemically induced carcinogenesis in rat liver, gradually increased to extremely high levels in tumors even after 75 days when the diet of the animals was changed to a normal one. In rats fed 3'-Me-DAB plus DSF, GT-ase activity increased for the greater part of 80 days, gradually leveled off around the 100th day, and returned to almost normal levels when the rats were given a normal diet after 100 days. We concluded that DSF 1) did not interfere with 3'-Me-DAB-induced proliferation of preneoplastic cells and the increase in GT-ase associated with this reversible adaptation to the influx of 3'-Me-DAB; and 2) inhibited malignant transformation and, consequently, prevented the formation and proliferation of neoplastic cells and the increase in constitutive GT-ase related to neoplasia.

gamma-Glutamyltransferase, a common marker of human epithelial tumors?

Having previously established gamma-glutamyltransferase (GGT) as a marker of experimental carcinogenesis in rat liver, we investigated whether human tumors differ from their tissue or origin by showing a higher activity or different localization of this enzyme histochemically. We found such differences in each of the human carcinomas we examined. The presence of GGT activity in carcinomas arising in organs normally containing little (tongue) or no GGT activity (larynx, urinary bladder, and esophagus) clearly distinguished cancerous from normal epithelium. In the breast, colon and prostate, GGT activity was normally present in a defined anatomical distribution bordering luminal surfaces. Carcinomas arising from these tissues showed a loss of the normal pattern of activity and contained cells with almost homogenous GGT activity in the cytoplasm. Such differences clearly distinguished carcinomatous from normal epithelium in these organs. The increased GGT activity observed in all nine carcinomas arising from seven different organs suggests that GGT may be a common marker of human epithelial tumors and staining for GGT may become a useful tool in the detection of human epithelial neoplasms.