In vivo cytogenetic investigations in bone marrow cells of rats, Chinese hamsters and mice treated with 6-mercaptopurine

Abstract

The chromosome-damaging effect of 6-mercaptopurine (6-MP) was investigated in bone marrow cells of rats, Chinese hamsters, and mice after single intraperitoneal injections of doses from 3.125 to 250 mg/kg, and after multiple applications of 10, 25, 50, and 125 mg/kg. The optimal time of investigation after single administration in these studies was 48 hrs after treatment for all 3 species. A nearly linear dose-response relationship with a low quadratic component was observed. The "critical dose" for all 3 species was 12.5 mg 6-MP/kg. However, mice generally demonstrated the highest sensitivity to the "clastogenic" effect of 6-MP. In agreement with results of acute toxicity studies, Chinese hamsters generally were less (and rats least) sensitive than the mouse to chromosomal damage induced by higher doses of 6-MP. After repeated treatment with low doses, the chromosome-damaging effect of 6-MP was less pronounced than after one single administration of a large dose equaling the total amount of substance applied in chronic treatment.