Influence of the Photodegradation of Azathioprine on DNA and Cells

Int J Mol Sci. 2022 Nov 20;23(22):14438. doi: 10.3390/ijms232214438.

Abstract

Azathioprine (AZA) is a pharmacologic immunosuppressive agent administrated in various conditions such as autoimmune disease or to prevent the rejection of organ transplantation. The mechanism of action is based on its biologically active metabolite 6-mercaptopurine (6-MP), which is converted, among others, into thioguanine nucleotides capable of incorporating into replicating DNA, which may act as a strong UV chromophore and trigger DNA oxidation. The interaction between azathioprine and DNA, before and after exposure to solar simulator radiation, was investigated using UV-vis spectrometry and differential pulse voltammetry at a glassy carbon electrode. The results indicated that the interaction of AZA with UV radiation was pH-dependent and occurred with the formation of several metabolites, which induced oxidative damage in DNA, and the formation of DNA-metabolite adducts. Moreover, the viability assays obtained for the L929 cell culture showed that both azathioprine and degraded azathioprine induced a decrease in cell proliferation.

Keywords: L929; azathioprine; photodegradation; spectrophotometry; voltammetry.

MeSH terms

  • Azathioprine* / pharmacology
  • DNA
  • DNA Adducts
  • Immunosuppressive Agents / pharmacology
  • Mercaptopurine* / pharmacology
  • Photolysis

Substances

  • Azathioprine
  • Mercaptopurine
  • DNA
  • Immunosuppressive Agents
  • DNA Adducts