Fluoranthene and phenantrene, two predominant PAHs in heat-prepared food, do not influence the frequency of micronucleated mouse erythrocytes induced by other PAHs

Polycyclic aromatic hydrocarbons (PAHs) occur in complex mixtures present in the human environment. Because of the carcinogenic properties of some of these PAHs, they raise concerns regarding health and food safety. Because the occurrence of benzo[a]pyrene, chrysene, benz[a]anthracene, and benzo[b]fluoranthene (PAH4) are considered markers for other genotoxic PAHs in foodstuffs, the European Union has put a maximum level of PAH4 in some foodstuffs. Fluoranthene (Flu) and phenanthrene (Phe), two other PAHs, are not classified as genotoxic and are abundant at rather high concentrations in food. Inasmuch as PAH4, Flu, and Phe are metabolized by the same cytochrome P450 pathway system, it is important to clarify whether Phe and Flu influence the genotoxicity of PAH4. We have analyzed the genotoxic response of Phe and Flu, separately and together, as well as in combination with different low doses of PAH4. In all experiments we used the flow cytometer-based micronucleus test in vivo. Phe and Flu, when administered separately, did not show any dose-related effect on the frequency of micronucleated polychromatic erythrocytes (fMNPCE). Nor did a mixture of Phe and Flu change the fMNPCEs. Phe and Flu did not significantly change the fMNPCE of PAH4-exposed FVB and BALB/c mice

Internal Doses of Glycidol in Children and Estimation of Associated Cancer Risk

The general population is exposed to the genotoxic carcinogen glycidol via food containing refined edible oils where glycidol is present in the form of fatty acid esters. In this study, internal (in vivo) doses of glycidol were determined in a cohort of 50 children and in a reference group of 12 adults (non-smokers and smokers). The lifetime in vivo doses and intakes of glycidol were calculated from the levels of the hemoglobin (Hb) adduct N-(2,3-dihydroxypropyl)valine in blood samples from the subjects, demonstrating a fivefold variation between the children. The estimated mean intake (1.4 μg/kg/day) was about two times higher, compared to the estimated intake for children by the European Food Safety Authority. The data from adults indicate that the non-smoking and smoking subjects are exposed to about the same or higher levels compared to the children, respectively. The estimated lifetime cancer risk (200/105) was calculated by a multiplicative risk model from the lifetime in vivo doses of glycidol in the children, and exceeds what is considered to be an acceptable cancer risk. The results emphasize the importance to further clarify exposure to glycidol and other possible precursors that could give a contribution to the observed adduct levels

Serum albumin adducts, DNA adducts and micronuclei frequency measured in benzo[a]pyrene-exposed mice for estimation of genotoxic potency

The environmental and food contaminant, benzo[a]pyrene {B[a]P, a polycyclic aromatic hydrocarbon (PAH)}, is classified as a human carcinogen by the International Agency for Research on Cancer. The carcinogenicity of B[a]P is linked to the formation of electrophilic metabolites, namely B[a]P-diol epoxides (BPDEs) occurring as stereoisomers. In this work, we quantified the metabolic formation of BPDE isomers and the genotoxic effect in B[a]P-exposed mice, with an aim to estimate the genotoxic potency of B[a]P per in vivo dose of its most potent metabolite [i.e. (+)-anti-BPDE]. The increase in frequency of micronuclei (fMN) in erythrocytes was measured as a biomarker for genotoxic effect. Covalent adducts to serum albumin (SA) and those to DNA from the BPDEs were analysed using liquid chromatography tandem mass spectrometry (LC–MS/MS), as adducts to histidine (BPDE-His-Pro) and deoxyguanosine (BPDE-dG), respectively. For the first time in animal experiments it was possible to resolve adducts to SA from (+)-anti-, (-)-anti- and (±)-syn-BPDE isomers by LC–MS/MS. The adduct levels in the protein were about 16 fmol/mg SA, which was orders of magnitude lower than that in the nucleic acid, 28 pmol/mg DNA, in mice exposed to 100 mg B[a]P per kg body weight (bw). Using SA adduct levels, the in vivo dose of (+)-anti-BPDE was calculated to be approximately 50 nM·h per mg B[a]P per kg bw. This allowed to make a preliminary estimate of the genotoxic potency as 2‰ fMN per μM·h of (+)-anti-BPDE. This estimate was compared to that from another food toxicant, glycidol, studied with similar methods, which indicated that the BPDE has several orders of magnitude higher genotoxic potency. The demonstrated approach on integrating biomarkers of internal dose of a causative agent and that of genotoxic effect for assessing genotoxic potency, using B[a]P as a model, has a potential for improving cancer risk assessment procedures for PAHs

High intake of fruit and vegetables is related to low oxidative stress and inflammation in a group of patients with type 2 diabetes

Background : Patients with type 2 diabetes have increased levels of oxidative stress and inflammation. A high fruit and vegetable intake may be beneficial. Objective : To study whether fruit and vegetable intake and levels of plasma antioxidants relate to markers of oxidative stress and inflammation in a group of patients with type 2 diabetes. Further, to investigate whether plasma antioxidants are good biomarkers for intake of fruit and vegetables. Design : Patients with type 2 diabetes were studied. Their dietary intake and levels of plasma antioxidants, and markers of oxidative stress and inflammation were analysed. Results : Fruit and vegetable intake was inversely related to oxidative stress. Plasma carotenoids were negatively correlated with inflammation. The plasma levels of -carotene and β-carotene showed strongly positive associations with fruit and vegetable intake. Conclusions : The results suggest that fruit and vegetable intake may decrease oxidative stress and inflammation in this group of patients. An increased intake of fruit and vegetables can therefore be beneficial for patients with type 2 diabetes, since these patients are documented to have raised oxidative stress and inflammation. The study support the usefulness of plasma -carotene and β-carotene as biomarkers for fruit and vegetable intake

High intake of fruit and vegetables is related to low oxidative stress and inflammation in a group of patients with type 2 diabetes

Abstract Background: Patients with type 2 diabetes have increased levels of oxidative stress and inflammation. A high fruit and vegetable intake may be beneficial. Objective: To study whether fruit and vegetable intake and levels of plasma antioxidants relate to markers of oxidative stress and inflammation in a group of patients with type 2 diabetes. Further, to investigate whether plasma antioxidants are good biomarkers for intake of fruit and vegetables. Design: Patients with type 2 diabetes were studied. Their dietary intake and levels of plasma antioxidants, and markers of oxidative stress and inflammation were analysed. Results: Fruit and vegetable intake was inversely related to oxidative stress. Plasma carotenoids were negatively correlated with inflammation. The plasma levels of a-carotene and b-carotene showed strongly positive associations with fruit and vegetable intake. Conclusions: The results suggest that fruit and vegetable intake may decrease oxidative stress and inflammation in this group of patients. An increased intake of fruit and vegetables can therefore be beneficial for patients with type 2 diabetes, since these patients are documented to have raised oxidative stress and inflammation. The study support the usefulness of plasma a-carotene and b-carotene as biomarkers for fruit and vegetable intake

In Vivo Doses of Acrylamide and Glycidamide in Humans after Intake of Acrylamide-Rich Food

For assessment of cancer risk from acrylamide (AA) exposure through food, the relation between intake from food in humans and the in vivo doses (area under the concentration-time curve, AUC) of AA (AUC-AA) and of its genotoxic metabolite glycidamide (GA) (AUC-GA) is used as a basis for extrapolation between exposure levels and between species. In this study, AA-rich foods were given to nonsmokers: a high intake of 11 mu g AA/kg body weight (bw) and day for 4 days or an extra (medium) intake of 2.5 mu g AA/kg bw and day for a month. Hemoglobin (Hb)-adduct levels from AA and GA, measured in blood samples donated before and after exposures, were used for calculation of AUC-AA and AUC-GA using reaction rate constants for the adduct formation measured in vitro. Both AA- and GA-adduct levels increased about twofold after the periods with enhanced intake. AUC for the high and medium groups, respectively, in nanomolar hours per microgram AA per kilogram bw, was for AA 212 and 120 and for GA 49 and 21. The AA intake in the high group was better controlled and used for comparisons with other data. The AUCs per exposure dose obtained in the present human study (high group) are in agreement with those previously obtained at 10(2) times higher exposure levels in humans. Furthermore, the values of AUC-AA and AUC-GA are five and two times higher, respectively, than the corresponding values for F344 rats exposed to AA at levels as in published cancer bioassays.