Yau T M
Mech Ageing Dev. 1979 Sep;11(2):137-44. doi: 10.1016/0047-6374(79)90031-9.
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.
丙二醛(MA)是一种源自多不饱和脂肪酸的脂质过氧化产物,对体外培养的小鼠L5178Y淋巴瘤细胞系具有细胞毒性。使用胸苷或甲氨蝶呤抗性作为遗传标记,将细胞暴露于低至20微摩尔的MA中24小时,可产生可检测到的细胞毒性以及存活细胞中突变体数量的增加。在所测试的MA浓度范围(10 - 100微摩尔)内,诱导的突变频率呈剂量依赖性。在MA处理的细胞中也观察到显著的分裂延迟,这导致生长不平衡。有人提出,MA与DNA交联并通过易错修复系统使细胞发生突变。为了将MA的诱变程度与哺乳动物细胞中的其他诱变剂相关联,还给出了X射线照射诱导的L5178Y中胸苷抗性标记的突变频率。将简要讨论脂质过氧化与致癌作用以及各种衰老理论的关系。