Mutagenicity and cytotoxicity of malonaldehyde in mammalian cells.

Malonaldehyde (MA), a lipid peroxidation product derived from polyunsaturated fatty acids, is cytotoxic to a murine L5178Y lymphoma cell line cultured in vitro. Exposure of cells for 24 hours to as little as 20 microM MA produced detectable cytotoxicity as well as an increased number of mutants among survivors, using thymidine or methotrexate resistance as genetic markers. The induced mutation frequency, within the range of MA concentrations tested (10-100 microM), is dose-dependent. Significant division delay, which results in unbalanced growth, is also observed in MA-treated cells. It is suggested that MA crosslinks with DNA and mutagenizes cells through the error-prone repair system. In order to relate the degree of mutagenicity of MA in reference to other mutagenic agents in mammalian cells, the mutation frequency of the thymidine-resistance marker in L5178Y induced by X-irradiation is also presented. The significance of lipid peroxidation in relation to carcinogenesis and the various theories of aging will be briefly discussed.