Malondialdehyde, mutagenicity

Plastaras, J. P. Dedon, P. C. Marnett, L. J. Effects of DNA structure on oxopropenylation by the endogenous mutagens malondialdehyde and base propenal. Biochemistry 2002,41, 5033-5042. 

Marnett, L.J. Tuttle, M.A. (1980) Comparison of the mutagenicities of malondialdehyde and the side products fonned during its chemical synthesis. Cancer Res., 40, 276-282... 

Yonei, S. Furui, H. (1981) Lethal and mutagenic effects of malondialdehyde, a decomposition product of peroxidized lipids, on Escherichia coli with different DNA-repair capacities. Mutat. Res., 88, 23-32... 

Polyenoic acids also give rise to malondialdehyde, a reactive mutagenic compound, which can be reduced... 

Basu AK, Marnett LJ. 1983. Unequivocal demonstration that malondialdehyde is a mutagen. Carcinogenesis 4 331-333. 

Basu AK, Marnett LJ. 1984. Molecular requirements for the mutagenicity of malondialdehyde and related acroleins. Cancer Res 44 2848-2854. 

Szabad J, Soos I, Polgar G, et al. 1983. Testing the mutagenicity of malondialdehyde and formaldehyde by the drosophila mosaic and the sex-linked recessive lethal tests. Mutat Res 113 117-133. 

The solution structures of DNA duplexes containing the mutagenic lesions of benzo [a] pyrene-dtrihydroxybenz[a] anthracene, aminopyrene-dG, aminofluorene-dG and malondialdehyde-dG derivatives have been reported. In each case the lesion was shown to intercalate into the duplex causing only minimal disruption to the duplex structure. These structures have been used to study the nucleotide excision repair (NER) by the UvrABC nuclease system from E. coli of the bulky purine lesions. ... 

Malondialdehyde (MDA), a by product of lipid degradation, can react with cellular nucleophiles and can form MDA-MDA dimers. Bolh MDA and the MDA-MDA dimer are mutagenic in bacterial assays and Ihe mouse lymphoma assay (Riggins and Mamett 2001). 

Riggins, J. N., and Mamett, L. J. (2001). Mutagenicity of the malondialdehyde oligomerization products 2-(3 -oxo-T-propenyl)-malondialdehyde and 2,4-dihydroxymethylene-3-(2,2-dimethoxyethyl) glutaraldehyde in Salmonella. Mutat Res 497, 153-157. 

If the process of lipid peroxidation continues unimpeded, the consequences include the release of toxic breakdown products and the eventual destruction of the lipid component of biological membranes (S28). Such breakdown products include the aldehydes, malondialdehyde, 2-alkenals, and 4-hydroxyalkenals. A number of mammalian GST isoenzymes are highly efficient in the detoxification of these compounds (Dl). Indeed, 4-hydroxynonenal is one of the best GST substrates identified to date, and with one of the rat GST isoenzymes the K JK value obtained indicates that catalysis proceeds relatively close to the diffusion-controlled limit. Cholesterol-5,6-epoxide is a further example of a byproduct of lipid peroxidation, and the conjugation of GSH to this weakly mutagenic compound is catalyzed by certain GST (M18). 

It has been implied that secondary products of lipid autoxidation are mutagenic. Interest in this area of research was stimulated when Mukai and Goldstein (55), as well as others, reported that malondialdehyde elicited a mutagenic response by the Ames test. Since some evidence for DNA... 

The base hydrolysis of zebularine [l-(p-D-ribofuranosyl)-l,2-dihydropyrimidin-2-one] has been investigated ring opening to give 234 is followed by formation of the oxazolidinone 235 and malondialdehyde, and it was theorised that the production of malondialdehyde, a known mutagen, may account in part for the antitumour activity of the nucleoside.321... 

Figure 2. Lipid peroxidation. Lipids containing polyunsaturated fatty acids (LH) are oxidized to form lipid peroxyl radicals (LOO ), which can generate mutagenic aldehydes such as malondialdehyde (MDA). Lipid hydroperoxides (LOOH) accumulate during lipid peroxidation. Vitamin E inhibits lipid peroxidation by quenching LOO radicals.

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