Purinethiols as feedback inhibitors of purine synthesis in ascites tumor cells.

The capacity of several purinethiol derivatives to produce prolongation of survival in mice bearing ascites-cell tumors and to produce feedback inhibition of purine synthesis in vivo in the tumor cells was investigated. Included were tumors susceptible and tumors resistant to treatment with 6-thioguanine. With susceptible tumors, certain of the purinethiols could increase survival of tumor-bearing mice as the sole treatment; some produced synergistic responses in combination with azaserine, and some did neither. Those purinethiols which could be converted to nucleotide form were found to produce feedback inhibition of purine synthesis. This group included 6-thioguanine, 6-mercaptopurine, and *-methylamino-6-purinethiol. Agents not converted to nucleotide and producing no feedback inhibition included 9-methyl thioguanine, 9-butyl thioguanine, 1-methyl-~-amino-6-purinethione, 6-methyl-~-amino-6-purinethiol, and probably 5'deoxythioguanosine. The data obtained are interpreted to indicate that the tumorinhibitory properties of these purinethiols are not due to feedback inhibition of purine synthesis. A thioguanine-resistant line of Ehrlich cells was found to be somewhat responsive to some of the other purinethiols.