title: The lipid peroxidation product 4-hydroxynonenal is a potent inducer of the SOS response.
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.
authors.affiliation: A.B. Hancock Jr. Memorial Laboratory for Cancer Research, Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232.
authors.forename: M
authors.initials: M
authors.lastname: Benamira
authors.forename: L J
authors.initials: LJ
authors.lastname: Marnett
mesh_terms: D000171:Acrolein / Q000494:pharmacology; D000447:Aldehydes / Q000494:pharmacology / Q000633:toxicity*; D015227:Lipid Peroxidation; D008315:Malondialdehyde / Q000494:pharmacology; D009153:Mutagens / Q000633:toxicity*; D009876:Operon; D013014:SOS Response, Genetics; D012486:Salmonella typhimurium / Q000187:drug effects
chemical_list: D000447:Aldehydes; D009153:Mutagens; D008315:Malondialdehyde; D000171:Acrolein; C012796:2-butenal; C027576:4-hydroxy-2-nonenal