Use of nucleosides in resistance to 6-thioguanine.

Ascites cell tumors were found to cleave thioguanine riboside relatively rapidly. In tumor cell lines lacking the ribonucleotide pyrophosphorylase necessary for formation of thioguanine ribonucleotide, thioguanine riboside was converted to nucleotide to a small extent. This nucleotide formation was enhanced, after a short time lag, by 9-methyl thioguanine. The nucleoside, adenine arabinoside, was not cleaved by the tumor cells and inhibited the cleavage of thioguanine riboside. However, adenine arabinoside was rapidly metabolized so that its influence was brief. Inhibition of thio guanosine cleavage by 9-methyl thioguanine resulted in an increase in incorporation of thioguanine into RNA but not into DNA. Since this did not increase the survival time of mice bearing the ribonucleotide pyrophosphorylase-lacking tumors, the im portance of achieving incorporation of thioguanine into DNA to obtain tumor in hibition would seem to have further support.