DNA damage and DNA adduct formation in rat tissues following oral administration of acrylamide

Manière, Isabelle; Godard, Thierry; Doerge, Daniel R.; Churchwell, Mona I.; Guffroy, Magali; Laurentie, Michel; Poul, J

doi:10.1016/j.mrgentox.2004.10.012

Cited by 92 publications

(58 citation statements)

References 45 publications

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“…CCl4-treated group showed sloughing and destruction of walls of seminiferous tubules necrosis, edema, and increase in fibers deposition (Figs. 21, 22, and 23), in accordance with Manierea et al (2005); Moustafa et al (2007)); Manjrekar et al (2008); Khan and Ahmed (2009);Hanafi (2012), and Khan (2012). These effects are due to the production of oxygen radicals in excess of the antioxidant capacity of the stressed tissue Yousef and Salama (2009).…”

Section: Resultsmentioning

confidence: 73%

The protective effect of N-acetyl cysteine against carbon tetrachloride toxicity in rats

Foaud

Kamel

El-Monem

2018

JoBAZ

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Background: Carbon tetrachloride (CCL4) is used as a solvent for oils and fats, as a refrigerant, and as a dry-cleaning agent. Inhalation of its vapors can depress central nervous system activity and cause degeneration of the liver and kidneys. Aim: The aim of this study was to investigate whether N-acetyl cysteine (NAC) has a protective effect on the toxicity caused by carbon tetrachloride. Methods: Male rats were used in this experiment. Animals were divided into five groups, 5 animals each: G1 received olive oil, G2 was treated with CCL4 (1 ml/kg body wt) dissolved in olive oil (1:1), G3 received NAC (300 mg/kg body wt), G4 received CCL4 plus NAC, and G5 received NAC for 1 week then administrated to the same treatment of G4. All administrations were performed by gavage and maintained for 4 weeks. Results: The present study revealed that administration of CCL4 caused a significant increase in liver marker enzymes Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), and alkaline phosphatase (ALP); also, malondialdehyde (MDA) content in the liver tissue was increased. However, serum total protein showed no change in all groups. Also, histopathological investigation of CCL4 on the liver, testis, and kidney showed different deleterious effects. Additionally, CCl4 induced a highly significant increase in the percentage of sperm shape abnormality and sperm DNA tail moment values. Alternatively, result revealed that the two routes of NAC administrations caused a significant decrease in liver marker enzymes as well as MDA contents; improvement in liver, kidney, and testes architecture; a significant decrease in the percentage of sperm head abnormalities; and decline in the DNA tail moment values. Conclusion: The present study pointed out the protective effect of NAC against the toxicity of CCL4.

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Section: Resultsmentioning

confidence: 73%

The protective effect of N-acetyl cysteine against carbon tetrachloride toxicity in rats

Foaud

Kamel

El-Monem

2018

JoBAZ

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“…Induction of DNA damage by AA as measured by the Comet assay has been reported in several tissues of mice or rats (Manière et al, 2005;Dobrzynska, 2007;Recio et al, 2010;Rothfuss et al, 2010) (Table 22). …”

Section: Genotoxicitymentioning

confidence: 93%

“…(Manière et al, 2005). Tissue samples from brain, liver and testes were analysed for N7-GA-Gua 5, at 24, 48, and 72 hours after dosing.…”

Section: Experimental Animal Studiesmentioning

confidence: 99%

Scientific Opinion on acrylamide in food

Publication¹

2015

EFS2

329

170

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EFSA was asked to deliver a scientific opinion on acrylamide (AA) in food. AA has widespread uses as an industrial chemical. It is also formed when certain foods are prepared at temperatures above 120 °C and low moisture, especially in foods containing asparagine and reducing sugars. The CONTAM Panel evaluated 43 419 analytical results from food commodities. AA was found at the highest levels in solid coffee substitutes and coffee, and in potato fried products. Mean and 95th percentile dietary AA exposures across surveys and age groups were estimated at 0.4 to 1.9 µg/kg body weight (b.w.) per day and 0.6 to 3.4 µg/kg b.w. per day, respectively. The main contributor to total dietary exposure was generally the category 'Potato fried products (except potato crisps and snacks)'. Preferences in home-cooking can have a substantial impact on human dietary AA exposure. Upon oral intake, AA is absorbed from the gastrointestinal tract and distributed to all organs. AA is extensively metabolised, mostly by conjugation with glutathione but also by epoxidation to glycidamide (GA). Formation of GA is considered to represent the route underlying the genotoxicity and carcinogenicity of AA. Neurotoxicity, adverse effects on male reproduction, developmental toxicity and carcinogenicity were identified as possible critical endpoints for AA toxicity from experimental animal studies. The data from human studies were inadequate for dose-response assessment. The CONTAM Panel selected BMDL 10 values of 0.43 mg/kg b.w. per day for peripheral neuropathy in rats and of 0.17 mg/kg b.w. per day for neoplastic effects in mice. The Panel concluded that the current levels of dietary exposure to AA are not of concern with respect to non-neoplastic effects. However, although the epidemiological associations have not demonstrated AA to be a human carcinogen, the margins of exposure (MOEs) indicate a concern for neoplastic effects based on animal evidence. © European Food SUMMARYFollowing a request from the European Commission, the Panel on Contaminants in the Food Chain (CONTAM Panel) was asked to deliver a scientific opinion on acrylamide (AA) in food. The Panel developed the draft scientific opinion which underwent a public consultation from 1 July 2014 to 15 September 2014. The comments received and how they were taken into account when finalising the scientific opinion were published in an EFSA Technical Report (EFSA, 2015).AA is a low molecular weight, highly water soluble, organic compound. It is used inter alia as an industrial chemical and in the production of polyacrylamides. Heightened concerns about exposure to AA arose in 2002 when it was discovered that it forms when certain foods are prepared at temperatures usually above 120 °C and low moisture. It forms, at least in part, due to a Maillard reaction between certain amino acids, such as asparagine, and reducing sugars. However, several other pathways and precursors have also been proposed to contribute to AA formation. AA forms in numerous baked or fried carbohydrate-rich f...

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“…Many toxic compounds such as polycyclic aromatic hydrocarbons [19], aromatic amine [20], heterocyclic aromatic amines [21,22], and acrylamides [23,24] were found to bind covalently to DNA after metabolic activation by intrinsic enzymes. Their carcinogenicity was reported to arise from the DNA damages resulting from the formation of DNA adducts.…”

mentioning

confidence: 99%

Liquid chromatography—tandem mass spectrometry analysis of the DNA adducts of aristolochic acids

Chan

Zheng

Cai

2007

J. Am. Soc. Mass Spectrom.

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Electrophilic attack of aristolactam-nitrenium ion by the C7 position to the exocyclic amino group in the DNA bases led to the formation of the major adducts. In this study, liquid chromatography coupled with electrospray ionization tandem mass spectrometry was applied to the study of DNA adducts of aristolochic acid (AA). When DNA (bases and CT-DNA) was incubated with AA, dG-AAI, dG-AAII, dA-AAI, dA-AAII, dC-AAI, and dC-AAII were detected and characterized. The dC adducts of AA were identified for the first time. The soft ionization technology allowed detection of the intact DNA adducts. High-resolution MS and MS-MS capabilities of a quadrupole time-of-flight mass spectrometer were shown to be efficient for DNA adducts analysis. DNA-AA adducts showed characteristic fragmentation patterns in MS-MS analysis. The dissociative loss of 116 Da from the DNA-AA adducts, which resulted from internal hydrogen transfer and cleavage at the CON glycosidic bond, provided a characteristic fragment for the structural elucidation. (J Am Soc Mass Spectrom 2007, 18, 642-650)

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DNA damage and DNA adduct formation in rat tissues following oral administration of acrylamide

Cited by 92 publications

References 45 publications

The protective effect of N-acetyl cysteine against carbon tetrachloride toxicity in rats

The protective effect of N-acetyl cysteine against carbon tetrachloride toxicity in rats

Scientific Opinion on acrylamide in food

Liquid chromatography—tandem mass spectrometry analysis of the DNA adducts of aristolochic acids

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