Lethal and mutagenic effects of malondialdehyde, a decomposition product of peroxidized lipids, on Escherichia coli with different DNA-repair capacities

Abstract

Lipid peroxidation, a chain reaction of oxidative deterioration of polyunsaturated fatty acids in lipids, has been implicated as a basic deteriorative reaction in various kinds of oxidative damage in living organisms. However, the relationship of lipid peroxidation to carcinogenesis remains tenuous. Recent studies have shown that there is a satisfactory correlation between mutagenesis and carcinogenesis. To clarify the relationship of lipid peroxidation to carcinogenesis, we attempted to examine the molecular characteristics, the repair mechanisms and the expression of mutations of DNA damage induced by lipid peroxides, secondary breakdown products and radicals produced during decomposition of lipid peroxides in Escherichia coli. The experiments dealt with the effect of malondialdehyde (MDA), one of the most important products of lipid peroxidation. In an E. coli mutagenesis system, we found that MDA is mutagenic in cells having active DNA-repair systems. The UvrB − and RecA − derivatives, however, are not mutable by the MDA treatment. The lethal action of MDA on the latter strains, however, is increased. These findings suggest that MDA induces interstrand cross-linking as can be deduced from the following experiments in vitro. (1) The reaction of MDA with DNA resulted in the formation of fluorescent products. The structure of the fluorescent chromophore — a conjugated amino-imino-propene compound — indicated that 1 mole of MDA reacts with 2 moles of amino groups present in DNA bases. (2) Heat-denaturation of native DNA resulted in a decrease in the yield of the fluorescent products. (3) The yield of the fluorescent products was also reduced by the pretreatment of DNA with mitomycin C. Therefore, it seems possible that lipid peroxidation leads to cellular mutagenesis, through DNA damage — such as by the fluorescent products induced by reaction with MDA.