Mutagenicity of the malondialdehyde oligomerization products 2-(3 '-oxo-1 '-propenyl)-malondialdehyde and 2,4-dihydroxymethylene-3-(2,2-dimethoxyethyl)-glutaraldehyde in Salmonella

Malondialdehyde (MDA), a byproduct of non-enzymatic lipid peroxidation and prostaglandin biosynthesis, has been shown to be a weak frameshift mutagen in Salmonella mutagenicity assays. Because it is a dialdehyde, MDA can unde rgo self condensation to form polymeric products. It is possible that these condensation products are highly mutagenic and have contributed to previou sly reported estimates of MDA mutagenicity. We synthesized two major MDA po lymerization products, (1) 2-(3'-oxo-1'-propenyl)-malondialdehyde [(MA)(2)] and (2) 2,4-dihydroxymethylene-3-(2,2-dimethoxyethyl)glutaraldehyde [(MDA) (3)Me-2] and tested their mutagenicity in the Salmonella frameshift tester strains hisD3052 and TA94 (hisD3052/pKM101). Analysis of the reversion rate s revealed both (MDA)(2) and (MDA)(3)Me-2 to be weak mutagens, approximatel y equipotent to MDA. Although both (MDA)(2) and (MDA)(3)Me-2 are mutagenic, the fact that their formation is thermodynamically unfavorable under physi ological conditions suggests they do not contribute significantly to the mu tagenicity of MDA solutions. (C) 2001 Elsevier Science B.V. All rights rese rved.