Sex-related Differences in the Disposition of the Potential Antitumor Drug, AT-125, in Mice
Sem, Philip Chan Chee
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AT-l25, an antitumor agent, was isolated from soil microorganism, streptomyces sviceus UC-5370, and was found to be active against P388 and L12l0 mouse leukemias, and against human breast and lung tumors transplanted into 'nude' mice. It was found that AT-125 was more toxic to female mice than male mice of both ICR end BDFl strains (Neil et aI, 1978). McGovren (1978a.) showed that female ICR mice had a slower AT-l25 plasma clearance rate than male mice. The objectives of this project were to investigate the plasma clearance of AT-l25 by male and female mice of the BDFl and CDFI mouse strains, to study the extent of urinary excretion of AT-l25 in ICR male and female mice and to perform a preliminary search for metabolites of AT-125 in mouse urine by means of bioautography. The results obtained were: (I) In BDFI and CDFI mouse strains, female mice were also slower in AT-125 clearance rates than males. Only small differences were seen in clearance between BDFl, CDFI and ICR strains. (2) Most of the injected dose of AT-l25 was recovered in the urine over 24 hours in both sexes of ICR mice and the t-test conducted on the urine data showed that there was no sex difference in the excretion of AT-125. (3) The results of the third study suggested that the urine of AT-125 treated ICR mice (both male and female) contained only unchanged AT-125 and no active metabolites.