Effects of thioguanine in mammals

HIOGUANINE, the 2-amino derivative of T 6-mercaptopurine (~-MP), was recently described as an effective inhibitor of the Crocker mouse sarcoma, S 180.39 5 This observation was an extension of earlier studies with purine derivatives in which the inhibitory effects of ~-M P had been found.394Since ~-M P had temporarily checked certain human leukemias,2 it was anticipated that the thioguanine analogue might be clinically effective.However, the known similarities in the properties of thioguanine and ~-M P implied that both substances act identically and suggested that clinical trials with the 2-amino derivative were not likely to uncover novel applications.Thus, both thioguanine and ~-M P inhibit growth in the wild-type strain of Lactobacillus casei, and the inhibitions they exert are blocked more or less competitively by the four natural purine bases.7.9~10Both inhibit a 2,6diaminopurine-resistant strain of L. casei and are ineffective against 6-~~-resistant cells.8.Q 9 Again, mouse tumors, such as S 180 and the L-1210 leukemia, are susceptible to each agent, but thioguanine does not inhibit 6-~~-resistant sublines of the same tumor.3.16Nonetheless, the present study points to prominent differences in the effects of thioguanine and ~-M P in various tissues of normal mammals.It could be supposed, therefore, that the two agents might differ in relative clinical value.The present work describes the toxic properties of thioguanine and compares these findings with those previously obtained with ~-M P .~, A preliminary report has been published.ls