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  • 1
    In: Chemical Research in Toxicology, American Chemical Society (ACS), Vol. 25, No. 2 ( 2012-02-20), p. 381-390
    Type of Medium: Online Resource
    ISSN: 0893-228X , 1520-5010
    Language: English
    Publisher: American Chemical Society (ACS)
    Publication Date: 2012
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  • 2
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 72, No. 8_Supplement ( 2012-04-15), p. 5732-5732
    Abstract: Acrylamide (AA), a genotoxic carcinogen (IARC class 2A), is a food contaminant formed by thermal treatment of food. The margin of exposure (MOE) of AA, representing the distance between the bench mark dose associated with 10% tumor incidence in rats and the estimated average human exposure, is considered to be low and of human health concern. After uptake, AA is partly converted by CYP450 2E1 into the genotoxic epoxide glycidamide (GA). GA forms DNA adducts, primarily at N7 of guanine (N7-GA-Gua). AA and its genotoxic metabolite GA are conjugated to glutathione and excreted via urine as mercapturic acids (MA), namely N-acetyl-S-(2-carbamoylethyl)-cysteine (AAMA), and N-acetyl-S-(2-hydroxy-2-carbamoylethyl)-cysteine (GAMA) which are used as biomarkers for exposure. Female Sprague Dawley (SD) rats were kept on an AA free diet. AA was given by gavage in a broad dosage range, covering single doses of 0.1-10,000 µg/kg bw. Formation of urinary MAs and of N7-GA-Gua DNA adducts in liver, kidney and lung was measured 16 h after application. The lowest dosage of 0.1 µg AA/kg bw did not result in significantly enhanced MA excretion, as compared to untreated controls, found to excrete about 0.8 nmol MA. Since the animals may have ingested at best 0.4 nmol AA/d with the diet, this findings suggests a background level of endogenously formed AA. At the lowest dosage (0.1 µg AA/kg bw), N7-GA-Gua adducts above the limit of detection (LOD, 0.2 adducts/10exp8 nucleotides) were not detected in any organ tested. At 1 µg/kg bw, enhanced adduct levels were found in kidney (around 1 adduct/10exp8 nucleotides) and lung ( & lt; 1 adduct/10exp8 nucleotides), but not in liver. At 10 and 100 µg/kg bw, adducts were found in all three organs, at levels not significantly different to those found at 1 µg AA/kg bw (about 1-2 adducts/10exp8 nucleotides). Taken together, the results of this in vivo study allow to conclude that exposure to single doses of AA in the range of human dietary exposure leads to N7-GA-Gua adduct levels in tissues of SD rats at the low end of steady state background DNA lesions of various origin in human and rat tissues. This study was supported by ISIC, the Institute for Scientific Information on Coffee. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5732. doi:1538-7445.AM2012-5732
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2012
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    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 3
    In: Molecular Nutrition & Food Research, Wiley, Vol. 56, No. 12 ( 2012-12), p. 1825-1837
    Type of Medium: Online Resource
    ISSN: 1613-4125
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2012
    detail.hit.zdb_id: 2160372-8
    SSG: 12
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  • 4
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 70, No. 8_Supplement ( 2010-04-15), p. 4692-4692
    Abstract: Acrolein (AC) is an α,ß-unsaturated aldehyde, classified by the IARC in group 3B (not classifiable as to its carcinogenicity to humans). It is supposed to be formed by heating of fat containing foods, via heat induced formation from glycerides/glycerol. Formation of AC from carbohydrates has also been discussed [Stevens and Maier, 2008]. Moreover, it also has been suggested that AC might be formed by endogenous metabolism as a side product of carbohydrate and/or amino acid turnover or by oxidative desamination of polyamines. Analytical determination of AC in foodstuffs is difficult, due to its high volatility and reactivity. Data on exposure and contents of AC in heat treated foods therefore are scarce. It is unclear, to which extent AC contributes to the overall exposure of heat induced biologically active compounds such as acrylamide (AA) and furan. AC forms 1,4-Michael type adducts of biomolecular targets with nucleophiles like sulfhydryl and amino groups. In the organism, AC is mainly conjugated to glutathione and excreted after degradation and reduction as the mercapturic acid (MA), N-acetyl-S-(3-hydroxypropyl)-cysteine (3-HPMA). In the present study, AC exposure and detoxification kinetics were investigated within the scope of a human study with 13 healthy volunteers ingesting a test meal of 150 g potato crisps. Urine was collected for up to 72 hours (12 time points) and MA contents were measured after purifying and enrichment by solid phase extraction (SPE) [Fuhr et al., 2006]. Levels of 3-HPMA and of MAs derived from AA (N-acetyl-S-(2-carbamoylethyl)-cysteine (AAMA)) and glycidamide (N-acetyl-S-(2-hydroxy-2-carbamoylethyl)-cysteine (GAMA)) were determined by liquid chromatography tandem mass spectrometry (LC-MS/MS), and urinary concentrations were standardized by reference to urinary creatinine. The maximal urine concentrations found for 3-HPMA, AAMA, and GAMA were (mean ± SD) 146 ± 86, 2.5 ± 0.8, 0.14 ± 0.07 µmol/g creatinine, respectively and elimination half lives were 5, 12, and 38 hours. The AA uptake with a 150 g meal of potato crisps was about 1 mg, equivalent to 12.4 µg/kg body weight. The predose values for the sum of AAMA and GAMA were 0.15, that for 3-HPMA 35.9 µmol/g creatinine. On the basis of the AUC values of MAs excreted in urine, the total excretion of 3-HPMA was about 15 times higher than that of AAMA plus GAMA. Thus, the exposure to AC from the test meal was at least one order of magnitude higher than exposure to AA. The question as to what extent AC exposure has to be taken into account when considering risk assessment by heat induced toxicants has not been addressed before. References: Fuhr, U. et al., Cancer Epidemiol Biomarkers Prev, 15(2); 266 Stevens, J. F., Maier, C. S., Mol. Nutr. Food Res., 52; 7 Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4692.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2010
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    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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