Determination of DNA adducts of malonaldehyde in humans: effects of dietary fatty acid composition

Abstract

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.

The Effect of n-6 Polyunsaturated Fatty Acid on Blood Levels of Malondialdehyde-Deoxyguanosine Adducts in Human Subjects

“…Thus this study therefore suggests that an increase in n-6 PUFAs causes an initial decrease in M 1 dG adduct levels, which is contrary to that shown by Fang et al [15] who compared n-6 PUFA and MUFA diets. We did keep MUFA constant at 15% of total energy whereas Fang et al had differing levels on both diets (10% on the PUFA diet and 16% on the MUFA diet).…”

“…However the increase in plasma PUFAs were not related to changes in plasma MDA or M 1 dG adduct levels. Only one volunteer showed an increase in MDA and it was actually reduced in three volun- Women did have higher levels of M 1 dG adducts than men by the end of the PUFA intervention, as reported by Fang et al [15], (2.70 per 10 7 ± 1.38 and 1.74 per 10 7 ± 1.51) but this was not significant (F 1.42, p 0.26). MDA levels were also higher in women (0.034 ± 0.010 compared with 0.007 ± 0.007) and this was significant (F 22.43 p 0.001).…”

“…Analysis of the data showed that the adducts were not in a steady state case despite this being the case for the plasma fatty acids. Other researchers have looked at different intervention lengths; Fang et al [15] had a 25 day intervention whereas de Kok et al had a 42 day intervention [30]. Thus, the differences observed between studies may be due, in part, to the intervention length if DNA adducts are rapidly removed from the body after a certain period of time which may vary between individuals, and for different adducts.…”

“…We have previously shown that inflammation of the gut is directly linked to elevated levels of M 1 dG [14]. Another study has suggested that a diet high in n-6 polyunsaturated fatty acids (PUFA) elevates M 1 dG adducts in human blood DNA, with women showing a slighter higher increase than men, [15] compared with a diet rich in monounsaturated fats. Nair et al [16] examined etheno adducts in a subset of these *Address correspondence to this author at the School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Byrom Street, Liverpool, L3 3AF, UK; Tel: 0044 (0) 151 231 2049; Fax: 0044 (0) 151 231 2170; E-mail: s.a.moore@ljmu.ac.uk volunteers and found greatly elevated etheno adduct levels in the women only.…”

Effects of xanthan–locust bean gum mixtures on the physicochemical properties and oxidative stability of whey protein stabilised oil-in-water emulsions

“…However, PUFA are highly susceptible to oxidation during storage, which creates various aldehydes and ketones products that render unacceptable odor and flavor in PUFA containing foods (McClements & Decker, 2008). In addition, lipid oxidation products, such as lipid peroxides, unsaturated aldehydes and malonaldehydes, and several cholesterol oxidation products (Sangeetha, Das, Koratkar, & Suryaprabha, 1990;Esterbauer, Schaur, & Zollner, 1990;Addis, 1986) have a negative impact on human health due to their cytotoxic and genotoxic effects (Kanner, 2007;Fang, Vaca, Valsta, & Mutanen, 1996). The rate of oxidation of PUFA can be retarded decreased by the addition of many synthetic or natural antioxidants.…”