DNA damage and repair activity after broccoli intake in young healthy smokers

Abstract

Cruciferous vegetables contain compounds with antioxidant properties (e.g. carotenoids, vitamin C and folates) and can alter the activity of xenobiotic metabolism (i.e. isothiocyanates). These constituents may be particularly important for subjects who are exposed to free radicals and genotoxic compounds, including smokers. The aim of the study was to evaluate the effect of broccoli intake on biomarkers of DNA damage and repair. Twenty-seven young healthy smokers consumed a portion of steamed broccoli (250 g/day) or a control diet for 10 days each within a crossover design with a washout period. Blood was collected before and after each period. The level of oxidatively damaged DNA lesions (formamidopyrimidine DNA glycosylase-sensitive sites), resistance to ex vivo H(2)O(2) treatment and repair of oxidised DNA lesions were measured in peripheral blood mononuclear cells (PBMCs). We also measured mRNA expression levels of repair and defence enzymes: 8-oxoguanine DNA glycosylase (OGG1), nucleoside diphosphate linked moiety X-type motif 1 (NUDT1) and heme oxygenase 1 (HO-1). After broccoli consumption, the level of oxidised DNA lesions decreased by 41% (95% confidence interval: 10%, 72%) and the resistance to H(2)O(2)-induced DNA strand breaks increased by 23% (95% CI: 13%, 34%). Following broccoli intake, a higher protection was observed in subjects with glutathione S-transferase (GST) M1-null genotype. The expression level and activity of repair enzymes was unaltered. In conclusion, broccoli intake was associated with increased protection against H(2)O(2)-induced DNA strand breaks and lower levels of oxidised DNA bases in PBMCs from smokers. This protective effect could be related to an overall improved antioxidant status.

Effects of micronutrients on DNA repair

“…Increases in OGG1 activity were reported after coenzyme Q 10 [59], slow-release vitamin C (but not conventional vitamin C capsules) [60], carrots (but not carotenes, vitamin C or mandarin oranges) [58], kiwifruit [61] and a high fruit and vegetable diet [62]. There was no effect of broccoli [63], or a cocktail of Se, retinol, b-carotene, vitamin C and vitamin E [64]. After folate supplementation, surprisingly, a decrease was seen, but only in individuals who were relatively folate-deficient [65].…”

“…This is generally found to be very slow, taking up to 24 h to [63] complete, compared with the rapid rejoining seen in most cultured cells [11,55]. Supplementation with vitamin C [56], b-carotene, lycopene (but not lutein) [57] or carrots [58] apparently accelerated the rejoining process.…”

“…Guarrera et al [67] report a general tendency for increased expression after a flavonoidrich diet, and 'DNA and repair' gene sets were upregulated after a high fruit and vegetable diet or kiwifruit supplementation [68]; whereas Møller et al [69], Riso et al [63] and Collins et al [61] found no effect on expression of hOGG1 and other repair genes. Premkumar et al [70] studied protein concentrations and found, in breast cancer patients receiving tamoxifen, an increase in the amount of PARP after supplementation with coenzyme Q 10 , riboflavin and niacin.…”

Comet assay to measure DNA repair: approach and applications

“…An increase in BER was reported with slow-release vitamin C capsules in a 4-week placebo-controlled trial (Guarnieri et al, 2008). There was no significant effect of intervention with a mix of selenium, retinol, β-carotene, vitamin C, and vitamin E for 6 weeks (Caple et al, 2010), nor after a broccoli-rich diet for 10 days in a crossover trial (Riso et al, 2010). A diet rich in fruits and vegetables (600 g/day) resulted in no effect on BER (Guarnieri et al, 2008), whereas a similar study of the effects of antioxidant-rich fruits and vegetables (Brevik et al, 2011b) showed a significant increase in BER (and a smaller, non-significant increase with three green kiwifruits/day).…”

Genome-Wide DNA Methylation Profiling in Dietary Intervention Studies: a User’s Perspective

“…The study was placebo-controlled, with a 20-day washout period between placebo-and broccoli-diet interventions. Blood was taken before and after both intervention periods, providing four DNA samples per volunteer over a period of about 6 weeks (study details in [58]). All 12 DNA samples were analyzed on one 450k bead chip, thus avoiding problems associated with batch affects.…”