Pharmacology of 6-Thioguanine in Man1

6-Thioguanine (6-TG) was administered to 15 patients with acute leukemia and to 9 with solid tumors in 32 experiments, as part of Phase I testing of 6-TG. 6-TG and metabolites were measured by labeling the 6-TG with radiosulfur. The levels of 6-TG and metabolites were measured in blood and urine after p.o. and i.v. dosage. Incorporation into DNA and RNA of the bone marrow was measured. Blood levels of 6-TG were higher after administration of i.v. dosages than after equal p.o. doses were given the same patients. Blood levels and incorporation into bone marrow DNA were higher with the higher doses but depended more upon the growth status of the marrow than upon dose level. Incorporation into DNA of the marrow was usually very small after administration of a single dose of 6-TG, but after 5 daily doses the guanine of the DNA was largely replaced by 6-TG. This indicates that most cells were caused to enter DNA synthesis in the 5-day period.