Studies on the relationship between hemoglobin and DNA adducts of malonaldehyde and their stability in vivo

Carcinogenesis. 1993 Apr;14(4):705-8. doi: 10.1093/carcin/14.4.705.

Abstract

The stability of the adducts of malonaldehyde (MA) to N-terminal valine in hemoglobin (Hb) and to guanine at N1,N2 in liver DNA was determined in vivo. Mice were injected with radiolabeled or unlabeled MA and the decay of the levels of Hb and DNA adducts was determined using the N-alkyl Edman method and the 32P-postlabeling assay respectively. The rate of adduct formation was much higher towards valine in Hb than towards guanine in DNA. The highest level of adducts to valine was observed 4 h after the treatment, whereas the corresponding level for guanine was after approximately 120 h. The adduct to guanine in DNA was significantly more stable. The estimated half-lives of the adduct to N-terminal valine in Hb and for the adduct to guanine in DNA were approximately 6 and approximately 12.5 days respectively. The persistence of DNA adducts from MA in liver indicates that this type of adduct is poorly recognized by DNA repair enzymes and thus may accumulate during chronic exposure.

Publication types

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

MeSH terms

  • Animals
  • DNA / metabolism*
  • Guanine / metabolism
  • Half-Life
  • Hemoglobin A / metabolism*
  • Liver / metabolism
  • Male
  • Malondialdehyde / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Valine / metabolism

Substances

  • Malondialdehyde
  • Guanine
  • DNA
  • Hemoglobin A
  • Valine