THIOPURINE NUCLEOTIDE SYNTHESIS IN A 6-MP-RESISTANT SUBLINE OF THE EHRLICH ASCITES CARCINOMA AND GROWTH INHIBITION BY CERTAIN ANTIMETABOLITES

Abstract

A 6-MP-resistant subline of the Ehrlich ascites carcinoma has been characterized as cross-resistant to thioguanine and is more sensitive to azaserine than the parent tumor line. The resistant subline has retained the sensitivity to amethopterin shown by the parent tumor line. 6-MP riboside was no more effective than 6-MP in inhibiting the growth of the resistant cells.It was shown previously that cells of this resistant subline, in contrast to cells of the parent line, were unable to synthesize 6-MP nucleotide from a test dose of 6-MP injected into the ascitic fluid. In the present study it was shown that resistant cells were also unable to convert 6-MP riboside or thioguanine to their nucleotide derivatives, both of which were synthesized by the 6-MP-sensitive parent line of tumor cells. Similarities observed in the metabolism of 6-MP and 6-MP riboside and in their chemotherapeutic effects were probably due to the extensive hydrolysis of 6-MP riboside which took place in both ascites tumors.