γ-Glutamyltransferase and the Inhibition of Azo Dye-Produced Neoplasia by Concomitant Administration of Disulfiram23

Abstract

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 stabilized 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 γ-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 of 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.