Development of monoclonal antibodies to the malondialdehyde-deoxyguanosine adduct, pyrimidopurinone

Chem Res Toxicol. 1997 Feb;10(2):172-80. doi: 10.1021/tx960120d.


Malondialdehyde (MDA), an endogenous product of lipid peroxidation and prostaglandin biosynthesis, is mutagenic in bacterial and mammalian cells and carcinogenic in rats. In order to determine whether MDA-modified bases are formed in nucleic acids in vivo, sensitive immunoassays to detect MDA-DNA and MDA-RNA adducts are being developed in our laboratory. Murine monoclonal antibodies reactive with the MDA-deoxyguanosine adduct 3-beta-D-erythro-pentofuranosylpyrimido[1,2-alpha]purin-10(3H)-one (M1G-R) were prepared and characterized. Several MDA-modified nucleosides and deoxynucleosides and structural analogs were synthesized and characterized and were compared as competitive inhibitors in enzyme-linked immunosorbent assays (ELISAs). Less than 5 fmol of M1G in MDA-modified DNA was detected in a direct ELISA, and antibody binding to the modified DNA was competitively inhibited by free M1G-dR. DNA from Salmonella typhimurium treated with concentrations of MDA that induce reversion to histidine prototrophy was enzymatically digested, and M1G-dR was quantitated by competitive ELISA. Over a range of MDA concentrations from 10 to 40 mM, the level of M1G residues in bacterial DNA increased from 0.2 to 2.5/10(6) base pairs.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acrolein / pharmacology
  • Animals
  • Antibodies, Monoclonal / biosynthesis*
  • Antibodies, Monoclonal / chemistry
  • Binding Sites, Antibody
  • Binding, Competitive / immunology
  • DNA / metabolism
  • DNA Adducts / immunology*
  • DNA Adducts / pharmacology
  • DNA, Bacterial / analysis
  • Deoxyguanosine / analogs & derivatives*
  • Deoxyguanosine / immunology*
  • Deoxyguanosine / pharmacology
  • Hybridomas / chemistry
  • Hydrolysis
  • Malondialdehyde / immunology*
  • Malondialdehyde / pharmacology
  • Mice
  • Mice, Inbred BALB C
  • Salmonella typhimurium / genetics


  • Antibodies, Monoclonal
  • DNA Adducts
  • DNA, Bacterial
  • Malondialdehyde
  • Acrolein
  • 3-(2'-deoxyribofuranosyl)pyrimido(1,2-a)purin-10(3H)-one
  • DNA
  • Deoxyguanosine