The Lethality and Toxicity of Intravenously Administered Mercaptopurine (NSC 755) in BDF1 Mice

摘要

The lethality of mercaptopurine (NSC 755), administered by intravenous injection was determined in male and female BDF(1) mice using a single dose or a five consecutive daily dose schedule. In subsequent studies the toxicity of mercaptopurine was determined using the LD50, LD10, and 1/2 LD10 via the same injection schedule and route as that used in the lethality studies. The extent of recovery from treatment induced toxicity was assessed by comparison of both clinical and histological changes observed between those animals sacrifced two days after the last injection versus those sacrificed after 14 treatment free days. Drug-related intoxication was characterized histologically by adverse changes in liver, bone marrow, gastrointestnal tract and vaious lymphoid tissues. Hematological findings of suppressed erythroid activity correlated well with morphological abnormality. The multiple dose exposure to mercaptropurine was shown to be more effective in producing intoxication. Recovery from drug-induced toxicity was observed as a reduction in the incidence and severity of abnormality in mice surviving to termination of the study.