DNA MODIFICATION INDUCED BY 6-MERCAPTOPURINE RIBOSIDE IN MURINE EMBRYOS

The cytostatic drug 6-mercaptopurine riboside (6-MPr) was investigated in mice in order to test the hypothesis that the teratogenicity of th is antimetabolite is paralleled by an incorporation into the DNA of th e embryos during organogenesis. DNA modification in the embryos was an alysed 4 h following s.c. administration of [S-35]-labelled 6-MPr to t he dams on day 11 of pregnancy. The DNA of the embryos was isolated an d hydrolysed to the bases by formic acid. Following separation by cati on-exchange HPLC 6-thioguanine was found in the hydrolysate. Quantitat ion was performed by liquid scintillation counting. Evaluations of 6 d oses in the range of 8-25 mg/kg were performed. An incorporation rate of 6-thioguanine from 32-56 pmol per mu mol guanine was found in the D NA of the embryos. These findings suggest that, similar to the previou sly studied alkylating agents, the teratogenicity of 6-MPr may be, at least in part, induced via DNA modification of the embryos.