Date of Award
Master of Science
Six-mercaptopurine is a chemotherapeutic drug which has been used extensively in clinical research as well as biological and biochemical experimental studies.
Studies on the absorption, distribution, toxicity, and metabolism of 6-mercaptopurine (6-MP) in experimental animals and in the human have been reported in recent reviews.
The extreme toxicity of 6-MP and its analogs have been observed in various species. Phillips (1954) reported that toxicity occurs in rabbits at a dosage level of 10 to 15 mg/ kg bdy wt/day, while 100 mg/kg bdy wt/day may be required to produce similar effects in guinea pigs. According to Hamilton and Elion (1954), toxicity often appears in man at a dosage of 2.5 mg/kg bdy wt/day. The toxicity of this purine and its derivatives has imposed obvious limitations in their use for treatment of leukemia.
Studies in our laboratory during the past year have demonstrated that the chick can tolerate 1200-1800 mg/kg bdy wt/ day of 6-MP. The writer could find no report of any investigation which involved the chick in regard to the unusual relative high tolerance of this compound, nor any reference to the metabolic degradation of this purine or its derivatives in this species.
The present status of research in this area has indicated that the therapeutic effectiveness of 6-MP and other purine derivatives, may be potentiated in man. It has been established that the end product of purine metabolism in man and in the chick is uric acid, although it is excreted in much larger amounts in the chick. In view of the chick's normal high tolerance for 6-MP, it seems logical to assume that this species may possess a mechanism which enables it to normally detoxify the oxidative metabolic end-products associated with the degradation of 6-MP and other derivatives more efficiently than man or other previously studied species.
R. W. Lewis
Prairie View Agricultural and Mechanical College
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Date of Digitization
John B Coleman Library
City of Publication
Mack, R. W. (1967). Relationship Between 6- Mercaptopurine Toxicity And Uric Acid Synthesis In The Chick. Retrieved from https://digitalcommons.pvamu.edu/pvamu-theses/1352