Determination of malonaldehyde-modified 2'-deoxyguanosine-3'-monophosphate and DNA by 32P-postlabelling

Carcinogenesis. 1992 Apr;13(4):593-9. doi: 10.1093/carcin/13.4.593.

Abstract

The 32P-postlabelling assay was used to determine adducts arising upon the reaction of malonaldehyde with 2'-deoxyguanosine-3'-monophosphate. The adducts formed were isolated, structurally characterized and identified as 3-(2-deoxy-beta-D-erythro-pentafuranosyl)pyrimido[1,2-alpha] purin-10(3H)-one. The kinetics of phosphorylation by T4 polynucleotide kinase was studied using 500 fmol of the synthesized standard and found to reach its maximum after 1 h of incubation. A 60% labelling efficiency was obtained at low concentrations of substrate. The adducted substrate was detected at the sub-femtomolar level. Sensitivity of the adducts towards nuclease P1 3'-dephosphorylation was also tested. The same adduct could be detected from calf thymus DNA that had been reacted in vitro with malonaldehyde, and in DNA isolated from mice treated with [14C]malonaldehyde. DNA adducts formed in vitro were isolated after enzymatic digestion to mononucleotides followed by HPLC fractionation or nuclease P1 digestion of normal nucleotides. A combination of the two procedures proved to be the method of choice for the isolation of the malonaldehyde-DNA adducts formed in vivo prior to applying the 32P-postlabelling assay.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chromatography, High Pressure Liquid
  • DNA / metabolism*
  • Deoxyguanine Nucleotides / metabolism*
  • Male
  • Malondialdehyde / pharmacology*
  • Mice
  • Mice, Inbred C57BL
  • Phosphorus Radioisotopes

Substances

  • Deoxyguanine Nucleotides
  • Phosphorus Radioisotopes
  • Malondialdehyde
  • DNA