Acrylamide catalytically inhibits topoisomerase II in V79 cells

Sciandrello, Giulia; Mauro, Maurizio; Caradonna, Fabio; Catanzaro, Irene; Saverini, Marghereth; Barbata, G

doi:10.1016/j.tiv.2009.12.010

Cited by 19 publications

(15 citation statements)

References 22 publications

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“…in plasma (Feng and Lu, 2011) and dopaminergic cells (Martyniuk et al, 2013). In V79 cells, AA was shown to interact with topoisomerase II (Sciandrello et al, 2010).…”

Section: Mechanisms and Modes Of Actionmentioning

confidence: 97%

Scientific Opinion on acrylamide in food

Publication¹

2015

EFS2

292

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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“…in plasma (Feng and Lu, 2011) and dopaminergic cells (Martyniuk et al, 2013). In V79 cells, AA was shown to interact with topoisomerase II (Sciandrello et al, 2010).…”

Section: Mechanisms and Modes Of Actionmentioning

confidence: 97%

Scientific Opinion on acrylamide in food

Publication¹

2015

EFS2

292

170

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“…The considerable number of TB patients in our country supports the fact that the use of early pharmacogenetic testing and a comprehensive clinical history may be useful in identifying patients with a high risk of suffering hepatotoxicity. This type of research further supports the use of personalized medicine in the treatment of TB and might be further carried out on the new anti-TB acrylamide-derived drugs [48] because the genotoxicity of this vinyl monomer is known [49].…”

Section: Discussionmentioning

confidence: 54%

Effect of gene–gene and gene–environment interactions associated with antituberculosis drug-induced hepatotoxicity

Chamorro

Castagnino

Aidar

et al. 2017

Pharmacogenetics and Genomics

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a Objectives This study evaluated the association between environmental factors and genetic variations in enzymes that metabolize antituberculosis (anti-TB) drugs [arylamine N-acetyltransferase 2, cytochrome P450 2E1 (CYP2E1), glutathione S-transferase theta 1 (GSTT1), and glutathione S-transferase mu 1] with antituberculosis drug-induced hepatotoxicity (ATDH). We also investigated the potential gene-gene and gene-environment interactions as well as their association with ATDH development in a population of hospitalized TB patients from Buenos Aires.Patients and methods We investigated 364 TB patients who received anti-TB drugs. Physicians collected demographic and clinical data to identify environmental risk factors for ATDH development. Polymorphisms were detected using gene sequencing, PCR, and PCR-restriction fragment length polymorphisms. A binary logistic regression analysis was carried out to compare the results of TB patients with and without the development of hepatotoxicity. The multifactor dimensionality reduction method was used to examine genetic and environmental interactions in association with ATDH.Results This study suggests that the slow acetylator profile [odds ratio (OR): 3.02; 95% confidence interval (CI): 1.82-5.00; P < 0.001], genotypes carrying the c2 variant (OR: 2.16; 95% CI: 1.33-3.51; P = 0.002) or the A4 variant of CYP2E1 (OR: 2.13; 95% CI: 1.06-4.29; P = 0.050), and female sex (OR: 1.94; 95% CI: 1.20-3.14; P = 0.006) were independent predictor variables for ATDH. Patients carrying the slow acetylator profile and the c2 variant showed an increased risk (OR: 7.068; 95% CI: 3.34-14.95; P < 0.001).We also identified a synergic interaction (epistasis) between GSTT1 and CYP2E1 associated with an increased risk for ATDH. A meaningful gene-environment interaction was associated with an increased risk of ATDH [testing balance accuracy = 0.675 (P = 0.001) and cross-validation consistency = 10/10].Conclusion ATDH is a severe and prevalent adverse drug reaction and leads to drug discontinuation in 11% of TB patients. Our study created a prediction model that properly classified the 67.5% of TB patients in their risk of developing ATDH. The considerable number of TB patients in our country supports the use of pharmacogenetic testing and a comprehensive clinical history to identify patients with a high risk of suffering hepatotoxicity. Pharmacogenetics and Genomics 00:000-000

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“…2. 3D structure of topoisomerase enzyme [Sciandrello et al, 2010]. The four exposed cysteines (Cys104, Cys216, Cys392 and Cys405) are named and indicated in licorice representation.…”

Section: Resultsmentioning

confidence: 99%

“…1. These are: human topoisomerase IIα [Sciandrello et al, 2010]; human-brain creatine kinase [Lü Z-R. et al, 2009]; human aldolase [Dobryszycki et al, 1999a;1999b]; human serum albumin [Ferguson et al, 2010]; human glyceraldehyde-3-phosphate dehydrogenase [Sakamoto & Hashimoto, 1985] and human enolase [Howland et. al., 1980].…”

Section: Proteinmentioning

confidence: 99%