We assessed the association of four diet quality scores with multiple cardio-metabolic outcomes among Guatemalan young adults experiencing the nutrition transition. We obtained cross-sectional dietary, demographic, anthropometric and cardio-metabolic risk factor data from 1220 Guatemalan adults (mean age 32·7 (sd 5·8) years) in 2002–4, and computed a Recommended Food Score (RFS), Not Recommended Food Score (NRFS), Food Variety Score (FVS) and the Dietary Quality Index-International (DQI-I). All four scores were correlated with energy intake (r 0·23–0·49; all P < 0·01), but had varying associations with socio-demographic characteristics, lifestyle factors and nutrient intakes. None of the scores was inversely associated with the metabolic syndrome or its components; rather some were positively associated with risk factors. Among both men and women the DQI-I was positively associated with BMI (kg/m2; β = 0·10, 95 % CI 0·003, 0·21 (men); β = 0·07, 95 % CI 0·01, 0·14 (women)) and waist circumference (cm; β = 0·02, 95 % CI 0·01, 0·03 (men); β = 0·02, 95 % CI = 0·01, 0·02 (women)). Among men, the RFS was positively associated with TAG (mg/l; β = 0·11, 95 % CI 0·02, 0·21) and glucose (mg/l; β = 0·13: 95 % CI 0·03, 0·22). We conclude that indices of diet quality are not consistently associated with chronic disease risk factor prevalence in this population of Guatemalan young adults.

Carotenoids are pigments found in fruits and vegetables. While high intakes of fruits and vegetables have been found to be associated with lower mortality, our objective is to investigate if total plasma carotenoids, via their antioxidant properties, are associated with mortality risk in a free-living elderly population. The ‘Epidemiology of Vascular Ageing’ (EVA) study (n 1389; 59–71 years) is a 9-year longitudinal study with six waves of follow-up. The association between baseline total plasma carotenoids and mortality was determined by Cox proportional hazards regression analyses. Low total plasma carotenoid level was significantly associated with all-cause mortality in men but not in women. After controlling for potential confounding factors, mortality risk increased significantly in men (P = 0·03) with plasma carotenoids in the lowest quintile compared with men with plasma carotenoids in the highest (relative risk 2·94 (95 % CI 1·21, 7·17)). A significant association between mortality by cancer and low plasma carotenoid level variable was also found in men (unit = 1 μmol/l; relative risk 1·72 (95 % CI 1·02, 2·86); P = 0·01). Associations between total plasma carotenoids and mortality risk remained statistically significant after taking into account: (1) plasma Se level, which previously was found associated with mortality in this population and (2) thiobarbituric acid-reactive substances level considered as an indicator of oxidative stress. By showing, prospectively, in a general healthy elderly population, that total plasma carotenoid levels were independently associated with mortality risk in men, the present study suggests that total plasma carotenoid levels could be a health indicator in elderly populations.

In the present study, the effects of trans-MUFA, elaidic acid (EA; 18 : 1-9t) and vaccenic acid (VA; 18 : 1-11t) on rat neutrophil functions were compared with those of cis-monounsaturated oleic acid (OA) (18 : 1-9c) and saturated stearic acid (SA; 18 : 0) (10–150 μm). Trans-fatty acids enhanced neutrophil phagocytic capacity, superoxide (O2∙-) and hydrogen peroxide production, and candidacidal activity. The same effects were observed for OA. Cells treated with trans-MUFA showed reduced production of NO∙, whereas those treated with OA showed an increase in production. Treatment with SA did not provoke significant effect on the parameters investigated. The increase in O2∙- production induced by MUFA was not observed when diphenyleneiodonium, an NADPH oxidase inhibitor, was added to the medium. This finding suggests that MUFA stimulate neutrophil NADPH oxidase activity. The addition of 3-[1-[3-(dimethylamino)propyl]-1H-indol-3-yl]-4-(1H-indol-3-yl)-1H-pyrrole-2,5-dione, a protein kinase C (PKC) inhibitor, and wortmannin, a phosphatidylinositol-3 kinase (PI3K) inhibitor, did not affect O2∙- production induced by MUFA. Therefore, the mechanisms by which MUFA stimulate NADPH oxidase are not dependent on PKC and do not seem to involve PI3K. Experiments using Zn2+, an inhibitor of NADPH oxidase H+ channel, indicated that MUFA activate the NADPH oxidase complex in rat neutrophil due to opening of H+ channel.

The aim was to identify the important sources of added sucrose and determinants of high intake, and to evaluate what impact a high proportion of energy from added sucrose has on the intake of foods and nutrients. The subjects consisted of children invited to the nutrition study within the Type 1 Diabetes Prediction and Prevention birth cohort and born in 2001 (n 846). Of these, 471 returned 3 d food records at 3 years of age. The average daily intake of added sucrose was 35 (sd 17) g (11·3 % of energy intake) and that of total sucrose was 41 (sd 18) g (13·3 % of energy intake). Sucrose added by manufacturers accounted for 82 %, naturally occurring sucrose for 15 % and sucrose added by consumers for 3 % of the total sucrose. Juice drinks, yoghurt/cultured milks, and chocolate and confectionery were the main contributors to added sucrose intake. Consumption of rye bread, porridge, fresh vegetables, cooked potatoes, skimmed milk, hard cheeses, margarine and fat spread as well as intake of most nutrients decreased across the quartiles of added sucrose (P < 0·05). Being cared for at home, having a father with a vocational school degree, having at least two siblings and a milk-restricted diet increased the risk for a high-sucrose diet. The study implied that a high proportion of added sucrose in the diet had mainly an unfavourable impact on the intake of recommended foods and key nutrients in Finnish children. The rationale for the recommendation to reduce the intake of refined sugars to ensure adequate intakes of nutrients seems reasonable.

Previously we had shown that neonatal leptin treatment programmes for both hyperleptinaemia and hyperinsulinaemia, which lead to leptin resistance and low expression of the hypothalamic leptin receptor (OB-Rb) of rats aged 150 d. Here we investigated in young post-weaned rats (age 30 d) if leptin treatment during lactation induces leptin and insulin resistance and if those changes are accompanied by changes in the suppressor of cytokine signalling-3 (SOCS-3) expression and serum adiponectin concentration. After delivery, the pups were divided into two groups: (1) a leptin group (Lep) that were injected with leptin daily (8 μg/100 g body weight subcutaneously) for the first 10 d of lactation; (2) a control (C) group, receiving saline. After weaning (day 21), body weight was monitored until the animals were age 30 d. They were tested for food intake in response to either leptin (0·5 mg/kg body weight intraperitoneally) (CL, LepL) or saline (CSal, LepSal) when they were aged 30 d. The CL group showed lower food intake, but no response was observed in the LepL group, suggesting leptin resistance. The Lep group had hyperleptinaemia (five-fold), hyperinsulinaemia (+42·5 %) and lower levels of serum adiponectin ( − 43·2 %). The hypothalamic expression of OB-Rb was lower ( − 22 %) and SOCS-3 was higher (+52·8 %) in the Lep group. We conclude that neonatal leptin treatment programmes for leptin resistance as soon as 30 d and suggests that SOCS-3 appears to be of particular importance in this event. In the Lep group, the lower serum adiponectin levels were accompanied by higher serum insulin, indicating a probable insulin resistance.

Dietary intake of long-chain n-3 PUFA has been reported to decrease several markers of lymphocyte activation and modulate monocyte susceptibility to apoptosis. However, most human studies examined the combined effect of DHA and EPA using relatively high daily amounts of n-3 PUFA. The present study investigated the effects of increasing doses of DHA added to the regular diet of human healthy volunteers on lymphocyte response to tetradecanoylphorbol acetate plus ionomycin activation, and on monocyte apoptosis induced by oxidized LDL. Eight subjects were supplemented with increasing daily doses of DHA (200, 400, 800, 1600 mg) in a TAG form containing DHA as the only PUFA, for 2 weeks each dose. DHA intake dose-dependently increased the proportion of DHA in mononuclear cell phospholipids, the augmentation being significant after 400 mg DHA/d. The tetradecanoylphorbol acetate plus ionomycin-stimulated IL-2 mRNA level started to increase after ingestion of 400 mg DHA/d, with a maximum after 800 mg intake, and was positively correlated (P < 0·003) with DHA enrichment in cell phospholipids. The treatment of monocytes by oxidized LDL before DHA supplementation drastically reduced mitochondrial membrane potential as compared with native LDL treatment. Oxidized LDL apoptotic effect was significantly attenuated after 400 mg DHA/d and the protective effect was maintained throughout the experiment, although to a lesser extent at higher doses. The present results show that supplementation of the human diet with low DHA dosages improves lymphocyte activability. It also increases monocyte resistance to oxidized LDL-induced apoptosis, which may be beneficial in the prevention of atherosclerosis.

Hypertension is a major risk factor for the development of CVD. Epidemiological studies have shown that low birth weight increases the risk of developing hypertension in adulthood. Hypertension increases the risk of suffering IHD and early findings provide evidence that hearts from prenatally protein-restricted, hypertensive, male offspring are more susceptible to cardiac dysfunction following ischaemic events. Hypertension and abnormalities in cardiac function following ischaemia–reperfusion in the human population are treated therapeutically with β-adrenergic antagonists. We hypothesised that increased susceptibility to myocardial ischaemia–reperfusion injury in prenatally programmed offspring may be due to sympathetic hyperactivity. Pregnant Wistar rats were fed control or low-protein (maternal low protein; MLP) diets throughout gestation. At age 6 months, hearts were rapidly excised and retro-perfused using the Langendorff apparatus, to assess isolated cardiac function following stimulation with increasing doses of the non-specific β-agonist isoproterenol. Baseline heart rates were similar in control and MLP-fed offspring. With significant diet × sex interactions (P < 0·01) maximum heart rate response following isoproterenol infusion was significantly longer in MLP than control. Prenatal diet had no effect on maximal left ventricular developed pressure (LVDP) response, but the LVDP isoproterenol response was significantly longer in duration in MLP-exposed male offspring (diet × sex P < 0·001). Myocardial mRNA expression of β2-adrenergic receptors was increased in 2-week-old female MLP offspring only (P < 0·049). In conclusion, maternal protein restriction programmes cardiac sympathetic activity in a sex-specific manner, and may explain increased susceptibility to ischaemia–reperfusion injury in males subject to fetal undernutrition.

Dietary fish oil is considered to have anti-inflammatory effects based primarily on its effects on T-cell proliferation and IL-2 secretion. Its effects on the secretion of T helper (Th) 1-type cytokines vary and few studies have examined its effects on the secretion of Th2-type cytokines. In the present study, we examined the effects of dietary fish oil on the secretion of Th1 and Th2-type cytokines by splenocytes and the mechanism by which dietary fish oil affects Th2-type cytokine secretion. Mice were fed diets supplemented with 18 % fish oil (w/w) +2 % maize oil or 20 % maize oil for 6 weeks. Spleen cells, isolated splenic T cells and accessory cells (splenocytes depleted of T cells) were stimulated with anti-CD3/anti-CD28. The secretion of interferon (IFN)-γ, TNF-α, IL-4 and IL-10 was measured by ELISA. Dietary fish oil decreased the secretion of IFN-γ and TNF-α by total splenocytes and isolated T cells. In contrast, dietary fish oil increased the secretion of IL-4 by total splenocytes but had no effect on IL-4 secretion by isolated T cells. When isolated T cells were cultured with CD11b+ cells (mainly macrophages), cells from mice fed the fish oil diet secreted more IL-4 than cells from mice fed the maize oil diet. These results demonstrate that dietary fish oil directs cytokine secretion by splenocytes towards a Th2 phenotype and that the effects of dietary fish oil on the secretion of a Th2-type cytokine are mediated by its effect on CD11b+ accessory cells.

Rapid postnatal growth in low-birth weight infants increases the risk of hypertension, CHD and type 2 diabetes in adult life. To provide validated tools to study the growth in South Asian infants, we evaluated two published equations to measure total body water (TBW) and fat-free mass (FFM) based on anthropometry in 6- to 24-month-old infants, using 2H2O dilution. In a method-comparison study in seventy-eight infants aged 6–24 months (forty-two girls and thirty-six boys) from the urban poor attending an immunisation clinic of a hospital in Kolkata, we measured their length to the nearest 0·1 cm, weight to the nearest 10 g and TBW using 2H2O dilution. The calculated TBW in kg (TBWkg) and FFM in kg (FFMkg) using two equations based on the length and weight were each compared with TBWkg and FFMkg calculated from 2H2O dilution. The mean FFMkg were 7·31 (sd 1·11), 7·13 (sd 1·08) and 7·26 (sd 1·13) by the 2H2O dilution method, and the anthropometry equations of Mellits and Cheek (AN-1) and Morgenstern et al. (AN-2), respectively. The mean of the paired difference in FFMkg was 0·18 (sem 0·06) and 0·04 (sem 0·07) between 2H2O, and AN-1 and AN-2, respectively. There is a good agreement for FFM derived by AN-2 with 2H2O dilution. The former is 1 % lower than that obtained from the reference method (P = 0·28). The AN-2 equation is useful for evaluating FFM in infants in India.

A longitudinal study of 298 rural Bangladeshi infants found evidence of growth faltering starting at 3 months of age. Anthropometric status declined substantially in the first 2 years of life, with weight-for-height (WHZ) falling from − 0·49 to − 1·75, weight-for-age (WAZ) from − 1·18 to − 2·87 and height-for-age (HAZ) from − 1·00 to − 1·88. Higher concentrations of the acute-phase protein α-1-acid glycoprotein (AGP) and higher gut mucosal damage (as signified by raised lactulose:mannitol (L:M) ratios) were both associated with chronic malnutrition as indicated by poorer HAZ and WAZ scores (P = 0·011 and 0·005 for AGP and 0·039 and 0·019 for L:M ratio, respectively). Higher Hb levels were related to improved z-scores, while elevation of Giardia-specific IgM titre (GSIgM) was associated with poor WAZ and WHZ (P = 0·015 and 0·039, respectively). IgG did not show any significant association with z-scores and the L:M ratio did not correlate with any of the inflammation markers or Giardia infection. The prevalence of geohelminth infections was low (only 4 % in the total study period). However, the level of GSIgM indicated high endemicity of Giardia infection from early in life, although very few cysts were detected from stool samples. These findings suggest that rural Bangladeshi infants are being exposed to high levels of infection with concomitant gut damage and growth faltering.

Presently used dietary-assessment methods often present difficulties for researchers and respondents, and misreporting errors are common. Methods using information and communication technologies (ICT) may improve quality and accuracy. The present paper presents a systematic literature review describing studies applying ICT to dietary assessment. Eligible papers published between January 1995 and February 2008 were classified into four assessment categories: computerised assessment; personal digital assistants (PDA); digital photography; smart cards. Computerised assessments comprise frequency questionnaires, 24 h recalls (24HR) and diet history assessments. Self-administered computerised assessments, which can include audio support, may reduce literacy problems, be translated and are useful for younger age groups, but less so for those unfamiliar with computers. Self-administered 24HR utilising computers yielded comparable results as standard methods, but needed supervision if used in children. Computer-assisted interviewer-administered recall results were similar to conventional recalls, and reduced inter-interviewer variability. PDA showed some advantages but did not reduce underreporting. Mobile phone meal photos did not improve PDA accuracy. Digital photography for assessing individual food intake in dining facilities was accurate for adults and children, although validity was slightly higher with direct visual observation. Smart cards in dining facilities were useful for measuring food choice but not total dietary intake. In conclusion, computerised assessments and PDA are promising, and could improve dietary assessment quality in some vulnerable groups and decrease researcher workload. Both still need comprehensive evaluation for micronutrient intake assessment. Further work is necessary for improving ICT tools in established and new methods and for their rigorous evaluation.

In the absence of effective pharmacotherapy for diabetes there has been an increase in the use of, and research into, alternative treatment strategies. These include exercise, dietary interventions and the use of supplements including extracts of ginseng. Two separate, placebo-controlled, double-blind, cross-over studies investigating the effects of chronic ingestion of Panax ginseng (study 1 used G115, study 2 used Cheong Kwan Jang) on glycated Hb (HbA1c; study 1, n 18; study 2, n 11), fasting plasma insulin (study 1, n 17; study 2, n 12), fasting plasma glucose and postprandial response (following breakfast) (study 1, n 23; study 2, n 14) in healthy volunteers are reported. In both studies it was found that Panax ginseng had no effect on any gluco-regulatory parameter investigated. These results are not consistent with those reported for a diabetic sample (albeit using slightly different outcomes). These results would suggest that chronic use of Panax ginseng by non-diabetic individuals will have little long-term effect on glucose regulation. The benefits to glucose regulation associated with long-term ginseng use may only be present in populations with compromised glucose control; however, further research is needed to confirm such a speculation.

The aims of the present study were to assess dietary intake of saccharides in middle-aged adults, and to determine whether intakes of these sugar nutrients were related to self-reported memory performance. A population-based sample of 1183 men and women (aged 40–60 years) completed questionnaires assessing everyday memory function. Dietary intake status of saccharides was estimated using a self-completed, quantified FFQ. After controlling for demographic and health measures (for example, time spent exercising, smoking and alcohol consumption), saccharide intake was related to better self-reported memory functioning. Thus, longer-term intakes of saccharides through the usual diet may be positively related to perceived memory performance in mid-life.

The purpose of the present study was to test the usefulness of dish items selected in developing a dish-based FFQ (DFFQ) to be used for epidemiological studies in Korea. The dietary data of 6817 subjects from the 2001 Korean National Health and Nutrition Examination Survey were used for the analysis. The 24 h recall method was employed for the dietary survey. Initially, ninety-five dish items were selected in developing the DFFQ based on consumption frequency, contribution of selected nutrients and coverage of between-person variations. The usefulness of the selected ninety-five dish items was tested based on their degree of contribution in supplying nutrients in the cumulative percentage contribution (cPC), as well as on their degree of explanation for between-person variation in the cumulative regression coefficient (cMRC). According to the results, the ninety-five selected dish items accounted for an average of 92·3 % of seventeen nutrients consumed by the study subjects based on cPC estimation. The top twenty items among the ninety-five dish items covered 70 to 91 % of the between-person variation for the seventeen nutrients based on cMRC estimation. Thus, the results suggest that the ninety-five items would be useful in developing a FFQ for use in epidemiological studies of Koreans, within less than 10 % underestimation.

The aim was to investigate how blueberry husks and/or mixtures of probiotic strains (Lactobacillus crispatus DSM16743, L. gasseri DSM16737 and L. plantarum DSM15313 (LABmix), or Bifidobacterium infantis DSM15159 and DSM15161 (BIFmix)) affect colonic fermentation, caecal counts of lactobacilli, bifidobacteria and Enterobacteriaceae, body weight gain, and blood concentrations of carboxylic acids (CA) and ammonia in rats. Dietary fibres in blueberry husks were fermented to 61 % in colon, and the elevated faecal excretion of fibre and protein contributed to the high faecal bulking capacity (1·3). The caecal pool of CA was higher in rats fed blueberry husks than the fibre-free control (P < 0·05), and the propionic acid proportion was higher in the distal colon than in the control group (P < 0·05). Probiotics lowered the caecal amount of CA when added to blueberry husks (P < 0·001), while the propionic acid proportion was higher with LABmix (P < 0·01) than blueberry husks only. The propionic acid and butyric acid concentrations in blood were higher in rats fed blueberry husks and probiotics than those fed blueberry husks only (P < 0·01), implying that the absorption of these acids was facilitated by the bacteria. The caecal counts of lactobacilli, bifidobacteria and Enterobacteriaceae were lower in rats fed blueberry husks than the control diet (P < 0·05). The body weight gain was partly influenced by the caecal tissue and contents weights, and BIFmix decreased the ammonia concentration in blood (P < 0·05). We conclude that colonic fermentation is differentially affected by dietary fibre and probiotics, which may be of importance when developing foods with certain health effects.

The dietary lectin phytohaemagglutinin (PHA) induces gut growth and precocious maturation in suckling rats after mucosal binding. The present study investigated the dose range in which PHA provokes gut maturation and if it coincided with immune activation. Suckling rats, aged 14 d, were orogastrically fed a single increasing dose of PHA: 0 (control), 2, 10, 50 or 250 μg/g body weight (BW) in saline. The effect on gut, lymphoid organs and appearance of CD3+ (T-lymphocyte) and CD19+ (B-lymphocyte) cells in the small-intestinal mucosa was studied at 12 h (acute) and 3 d (late phase) after treatment. The low PHA doses (2 and 10 μg/g BW) induced intestinal hyperplasia without mucosal disarrangement but did not provoke gut maturation. Only the high PHA doses (50 and 250 μg/g BW) temporarily disturbed the intestinal mucosa with villi shortening and decrease in disaccharidase activities, and later after 3 d provoked precocious maturation, resulting in an increase in maltase and sucrase activities and decrease in lactase activity and disappearance of the fetal vacuolated enterocytes in the distal small intestine. Exposure to the high, but not to the low, PHA doses increased the number of mucosal CD19+ and CD3+ cells in the small intestine after 12 h, a finding also observed in untreated weaned rats aged 21–28 d. In conclusion, there was a dose-related effect of PHA on gastrointestinal growth and precocious maturation that coincided with a rapid expansion of mucosal B- and T-lymphocytes, indicating a possible involvement of the immune system in this process.

Early childhood growth retardation persists in developing countries despite decades of nutritional interventions. Adequate food is necessary, but not sufficient, to ensure normal growth where there is ubiquitous exposure to infection. Pathways associated with infection, small intestinal mucosal damage and chronic immunostimulation remain largely undemonstrated in countries other than The Gambia. We conducted a longitudinal study of one squatter and one middle-class group (n 86, 3–18 month olds) to assess these relationships in Nepal. Growth, mucosal damage index (MDI; urinary lactose:creatinine ratio adjusted for body weight), morbidity reports, and blood concentrations of albumin, α-1-acid glycoprotein, IgG and Hb, were recorded monthly. Growth status worsened dramatically from 6 to 18 months, with squatters more stunted (height-for-age Z-score (HAZ), P < 0·001) and underweight (weight-for-age Z-score (WAZ), P = 0·009) than middle class. IgG increased with age, was elevated in squatter children, and negatively related to WAZ (P = 0·034). MDI showed significant negative associations with growth performance, explaining 9 and 19 % of height and weight deficits (ΔHAZ, P = 0·004; ΔWAZ, P < 0·001). Unexpectedly, these associations were weaker in squatter children, namely in the group which showed poorer growth, elevated morbidity, greater pathogen exposure (IgG) and higher MDI (P < 0·001). In Nepal, as in The Gambia, children exhibit poor growth, mucosal damage and immunostimulation. The relative impact of pathways associated with infection and undernutrition may, however, differ across socio-economic groups: in poorer children, the impact of mucosal damage and immunostimulation could be masked by nutritional constraints. This has important implications for public health interventions.

Several reviews of behavioural studies have concluded that some foods may have beneficial effects on cognitive performance. The present review summarises findings from studies using event-related potentials to investigate the food effects on brain activity underlying cognition. Despite initial positive indications from observational studies, subsequent studies with a within-subject design have not consistently confirmed these effects. This could be due to several factors, e.g. the use of attention tests (in contrast to memory tests employed in behavioural studies) and the lack of a control condition in some instances. Future studies could benefit from measuring cognitive performance with more difficult tests that tap into cognitive domains other than attention, using an appropriately controlled cross-over design, and a more systematic variation and complete description and characterisation of the food intervention.

Vitamin K acts as a cofactor during the γ-carboxylation of vitamin K-dependent proteins. Undercarboxylated osteocalcin (ucOC) is a suggested biomarker of vitamin K status. The +2255 polymorphism of the vitamin K epoxide reductase gene (VKORC1) was shown to be associated with the recycling rate of the active form of vitamin K. We investigated the association between dietary vitamin K intake and serum ucOC and hypothesized that this association might vary by VKORC1 genotype. ucOC and total intact osteocalcin (iOC) concentrations were quantified using specific ELISA tests in serum samples of 548 male and female participants (aged 18–81 years) of the Bavarian Food Consumption Survey II. ucOC was expressed relative to iOC (ucOC/iOC ratio). Dietary intake of vitamin K (phylloquinone and menaquinones) was estimated from three 24 h dietary recalls using previously published food composition data. The association between dietary vitamin K intake and ucOC/iOC ratio was analysed using linear and non-linear regression models. Median intakes of phylloquinone/menaquinones were 83·4/37·6 μg/d in men and 79·6/29·8 μg/d in women, respectively. As expected, vitamin K intake was significantly inversely associated with the ucOC/iOC ratio. The ucOC/iOC ratio differed significantly across variants of the +2255 polymorphism in the VKORC1 gene. Stratification by VKORC1+2255 genotype revealed that only in carriers of the GG genotype (39 % of all participants) did the ucOC/iOC ratio significantly decrease with increasing intake of vitamin K. Thus, the results show that the inverse association between dietary vitamin K intake and serum ucOC depends on a functionally relevant allelic variant of the VKORC1 gene.

Polycyclic aromatic hydrocarbons (PAH) are established cancer initiators that can be found in our food and environment. Some dietary phytochemicals are strong inhibitors of PAH-induced mutagenesis. The soya isoflavone genistein has been shown previously in our laboratory to be an inhibitor of PAH metabolite binding to DNA. In the present study, we investigated the effect of genistein on oxidative DNA damage induced by PAH in the non-tumorigenic breast cell line MCF10A. 7,12-Dimethyl-benz[a]anthracene (DMBA) can induce expressions of CYP1A1 and CYP1B1 which are known to be responsive to PAH. These enzymes, in turn, will metabolise the PAH into their ultimate carcinogenic forms. Genistein can significantly suppress the expressions within 5 μm. The comet assay indicated that DMBA introduced DNA damage to these cells, and co-treatment with genistein at 5 or 10 μm could alleviate the damage. In addition to the chelation of DMBA metabolites to DNA, flow cytometry results revealed that oxidation was also a factor of DNA damage. The oxidative DNA damage could be removed by co-treating with 10 μm-genistein. Because no increased oxidative DNA repair was observed, suppression on the cytochrome enzymes appeared to be the underlying mechanism.