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DNA modification induced by 6-mercaptopurine riboside in murine embryos

T Platzek1, R Schwabe, U Rahm

  • 1Max-von-Pettenkofer-Institut, Bundesgesundheitsamt, Berlin, Germany.

Chemico-Biological Interactions
|October 1, 1994
PubMed

Insights

The antimetabolite 6-mercaptopurine riboside (6-MPr) was found to incorporate into embryonic DNA during pregnancy. This DNA modification may contribute to the teratogenicity of 6-MPr.

Area of Science:

  • Developmental toxicology
  • Pharmacology
  • Molecular biology

Background:

  • 6-mercaptopurine riboside (6-MPr) is a cytostatic antimetabolite.
  • The teratogenic potential of 6-MPr requires further investigation.
  • Understanding drug-induced developmental toxicity is crucial for risk assessment.

Purpose of the Study:

  • To test the hypothesis that 6-MPr teratogenicity is linked to its incorporation into embryonic DNA.
  • To investigate DNA modification in mouse embryos following maternal administration of 6-MPr.

Main Methods:

  • Pregnant mice were administered [35S]-labelled 6-MPr on day 11 of gestation.
  • Embryonic DNA was isolated and hydrolyzed to bases using formic acid.
  • Cation-exchange HPLC and liquid scintillation counting were used to quantify 6-thioguanine incorporation.

Main Results:

  • 6-thioguanine, a metabolite of 6-MPr, was detected in the DNA hydrolysate of embryos.
  • Incorporation rates of 32-56 pmol 6-thioguanine per μmol guanine were quantified in embryonic DNA.
  • Significant DNA modification was observed in embryos exposed to 6-MPr.

Conclusions:

  • The findings suggest that 6-MPr can be incorporated into embryonic DNA during organogenesis.
  • DNA modification by 6-MPr may be a mechanism underlying its teratogenicity.
  • This mechanism is potentially similar to that of previously studied alkylating agents.

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