Fang J L, Vaca C E, Valsta L M, Mutanen M
Center for Nutrition and Toxicology, Department of Biosciences at NOVUM, Karolinska Institute, Huddinge, Sweden.
Carcinogenesis. 1996 May;17(5):1035-40. doi: 10.1093/carcin/17.5.1035.
The effects of dietary fatty acid composition on the endogenous formation of DNA adducts of malonaldehyde (MA), the major product of lipid peroxidation, were investigated in humans. A group of 59 healthy individuals of both sexes and different ages was initially fed a milk fat-based diet rich in saturated fatty acids for 14 days. Following this initial period, after which the group was considered homogeneous with respect to diet, 30 randomly chosen subjects were given a sunflower oil-based (rich in polyunsaturated fatty acids) (SO) diet and the remaining 29 individuals a low erucic acid rapeseed oil-based (rich in monounsaturated fatty acids) (RO) diet for 25 days. The fatty acid composition of plasma lipid fractions and the level of DNA adducts of MA in total white blood cells were then determined at the end of the SO and RO dietary periods. DNA adduct levels were measured by 32p-postlabelling using reversed-phase HPLC with on-line detection of radioactivity. Higher concentrations of polyunsaturated fatty acids in plasma triglycerides and higher levels of DNA adducts of MA were found in the subjects on the SO diet when compared with those in the RO dietary group. A large inter-individual variation in adduct levels was observed. The average adduct level in the SO diet group was 7.4 +/- 8.7 adducts/10(7) nucleotides (n = 23). This level was 3.6-fold higher than that found in individuals in the RO diet group (P < 0.001). Our results, in conjunction with the mutagenic and carcinogenic properties of MA, thus suggest the interaction of lipid peroxidation products such as MA with DNA as one plausible mechanism explaining the involvement of dietary fat in carcinogenesis.
研究了膳食脂肪酸组成对脂质过氧化主要产物丙二醛（MA）DNA加合物内源性形成的影响。一组59名不同年龄和性别的健康个体最初食用富含饱和脂肪酸的乳脂肪饮食14天。在这一初始阶段之后，该组在饮食方面被认为是同质的，随后30名随机选择的受试者食用富含多不饱和脂肪酸的葵花籽油（SO）饮食，其余29名个体食用富含单不饱和脂肪酸的低芥酸菜籽油（RO）饮食25天。然后在SO和RO饮食期结束时测定血浆脂质组分的脂肪酸组成和全白细胞中MA的DNA加合物水平。DNA加合物水平通过32P后标记法，采用反相高效液相色谱法在线检测放射性进行测定。与RO饮食组相比，SO饮食组受试者血浆甘油三酯中多不饱和脂肪酸浓度更高，MA的DNA加合物水平也更高。观察到加合物水平存在较大的个体间差异。SO饮食组的平均加合物水平为7.4±8.7个加合物/10（7）个核苷酸（n = 23）。这一水平比RO饮食组个体中发现的水平高3.6倍（P < 0.001）。我们的结果，结合MA的诱变和致癌特性，因此表明脂质过氧化产物如MA与DNA的相互作用是解释膳食脂肪参与致癌作用的一种合理机制。
