Lethal toxicity and myelotoxicity to mice of the combination of 6-thioguanine and 3-[(4-amine-2-methyl-5-pyrimidinyl)methyl]-1-(2-chloroethyl)-1-nitrosourea hydrochloride.
In order to determine the mechanism of therapeutic synergism elicited by a combination of 6-thioguanine and 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-1-(2-chloroethyl)-1-nitrosourea hydrochloride (ACNU) against various murine tumors, side effects of host animals due to the combination of these two drugs were examined. The combination toxicity index of these drugs given simultaneously was determined to be 1.5, i.e., this indicates that the combination of ACNU and 6-thioguanine is less-than-additive with respect to the lethal toxicity. More-over, this combination treatment appeared to be at least no more than additive with respect to bone marrow toxicities as judged on the basis of bone marrow cellularity and peripheral white blood cell counts. In addition, the effects of treatment schedules, which were clearly observed in the therapeutic effect, on the side effects due to this combination treatment were also examined. However, no specific decrease or increase in side effects on host animals on this specific treatment schedule or the other treatment schedule was seen.
D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D001853:Bone Marrow / Q000187:drug effects*; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D007970:Leukopenia / Q000139:chemically induced; D051379:Mice; D015376:Nimustine; D009607:Nitrosourea Compounds / Q000008:administration & dosage / Q000633:toxicity*; D013866:Thioguanine / Q000008:administration & dosage
D000970:Antineoplastic Agents; D009607:Nitrosourea Compounds; D015376:Nimustine; D013866:Thioguanine