The lipid peroxidation product 4-hydroxynonenal is a potent inducer of the SOS response

Mutat Res. 1992 Nov;293(1):1-10. doi: 10.1016/0921-8777(92)90002-k.

Abstract

An important aspect of bacterial mutagenesis by several difunctional carbonyl compounds appears to be the induction of the SOS system. We tested the ability of a series of carbonyl compounds to induce expression of the SOS-regulated umu operon in Salmonella typhimurium TA1535/pSK1002. SOS-inducing potencies varied widely among the carbonyl compounds tested. 4-Hydroxynonenal, a product of lipid peroxidation, was the most potent SOS-inducer, with maximal induction observed at concentrations of 0.1-1 microM. Acrolein, crotonaldehyde and methacrolein induced little increase over background umu expression. Malondialdehyde, another product of lipid peroxidation, was a very weak SOS-inducer with a maximal response induced at a concentration of 28 mM. Substitution at the alpha-position of malondialdehyde, which abolishes frameshift mutagenicity, did not abolish SOS-inducing activity. Substitution of the hydroxyl group of malondialdehyde and alpha-methyl-malondialdehyde by a better leaving group (benzoyloxy) resulted in an approximately 250-fold higher SOS-inducing potency. Comparison of the present results to literature reports on bacterial mutagenicity indicates a poor correlation of the two properties between different classes of difunctional carbonyl compounds and even within the same class of difunctional carbonyl compounds.

Publication types

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

MeSH terms

  • Acrolein / pharmacology
  • Aldehydes / pharmacology
  • Aldehydes / toxicity*
  • Lipid Peroxidation*
  • Malondialdehyde / pharmacology
  • Mutagens / toxicity*
  • Operon
  • SOS Response, Genetics*
  • Salmonella typhimurium / drug effects

Substances

  • Aldehydes
  • Mutagens
  • Malondialdehyde
  • Acrolein
  • 2-butenal
  • 4-hydroxy-2-nonenal