Chromosome aberrations in tunnel workers exposed to acrylamide and N-methylolacrylamide

Kjuus, Helge; Hansteen, Inger-Lise; Ryberg, David; Goffeng, Lars Ole; Øvrebø, Steinar; Skaug, Vidar

doi:10.5271/sjweh.886

Cited by 24 publications

(10 citation statements)

References 27 publications

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“…Of these, AAMA, its sulfoxide, and GAMA have been unequivocally confirmed in humans (9)(10)(11). Whereas there are many glutathione-S-transferases (GST) in humans and rodents, which may be involved in these metabolic steps, nonenzymatic formation of glutathione conjugates is also possible and has been reported for acrylamide (25,26). The role of GSTs in acrylamide metabolism in humans remains to be assessed.…”

Section: Introductionmentioning

confidence: 99%

In vivo Role of Cytochrome P450 2E1 and Glutathione-S-Transferase Activity for Acrylamide Toxicokinetics in Humans

Doroshyenko

Fuhr

Kunz

et al. 2009

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Acrylamide, a potential food carcinogen in humans, is biotransformed to the epoxide glycidamide in vivo. Both acrylamide and glycidamide are conjugated with glutathione, possibly via glutathione-S-transferases (GST), and bind covalently to proteins and nucleic acids. We investigated acrylamide toxicokinetics in 16 healthy volunteers in a four-period change-over trial and evaluated the respective role of cytochrome P450 2E1 (CYP2E1) and GSTs. Participants ingested selfprepared potato chips containing acrylamide (1 mg) without comedication, after CYP2E1 inhibition (500 mg disulfiram, single dose) or induction (48 g/d ethanol for 1 week), and were phenotyped for CYP2E1 with chlorzoxazone (250 mg, single dose). Unchanged acrylamide and the mercapturic acids N -acetyl-S-(2-carbamoylethyl)-cysteine (AAMA) and N-acetyl-S -(2-hydroxy-2-carbamoylethyl)-cysteine (GAMA) accounted for urinary excretion [geometric mean (percent coefficient of variation)] of 2.9% (42), 65% (23), and 1.7% (65) of the acrylamide dose in the reference period.Hemoglobin adducts increased clearly following the acrylamide test-meal. The cumulative amounts of acrylamide, AAMA, and GAMA excreted and increases in AA adducts changed significantly during CYP2E1 blockade [point estimate (90% confidence interval)] to the 1.34-fold (1.14-1.58), 1.18-fold (1.02-1.36), 0.44-fold (0.31-0.61), and 1.08-fold (1.02-1.15) of the reference period, respectively, but were not changed significantly during moderate CYP2E1 induction. Individual baseline CYP2E1 activity, CYP2E1*6, GSTP1 313A>G and 341T>C single nucleotide polymorphisms, and GSTM1-and GSTT1-null genotypes had no major effect on acrylamide disposition. The changes in acrylamide toxicokinetics upon CYP2E1 blockade provide evidence that CYP2E1 is a major but not the only enzyme mediating acrylamide epoxidation in vivo to glycidamide in humans. No obvious genetic risks or protective factors in xenobiotic-metabolizing enzymes could be determined for exposed subjects. (Cancer Epidemiol

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Section: Introductionmentioning

confidence: 99%

In vivo Role of Cytochrome P450 2E1 and Glutathione-S-Transferase Activity for Acrylamide Toxicokinetics in Humans

Doroshyenko

Fuhr

Kunz

et al. 2009

Cancer Epidemiology, Biomarkers &Amp; Prevention

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“…Acute neurotoxic effects were seen among Swedish workers in a tunnel construction project where NMA-based grouts were used (9). We have previously reported possible genotoxic (10) and neuro toxic (11) effects among Norwegian tunnel workers using NMAbased grouts. Among the Norwegian tunnel workers, we found indications of reversibility of several symptoms, such as skin-irritat ion, pares thesia, and pain in the hands when the workers were examined 16 months postexposure (11).…”

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confidence: 96%

Self-reported symptoms and neuropsychological function among tunnel workers previously exposed to acrylamide and N-methylolacrylamide

Goffeng¹,

Alvestrand²,

Ulvestad³

et al. 2010

Scand J Work Environ Health

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“…Acrylamid an L-Glutathion durch die Glutathion-S-Transferasen M1 und T1 und eine damit verbundene Modulation eines genetischen Risikos gemessen als Chromosomenaberrationen konnten bisher nicht eindeutig nachgewiesen werden [71]. Ex-vivo-Inkubationen von Acrylamid mit Blutproben unterschiedlicher GSTM1-und GSTT1-Aktivitäten zeigen keinen modulierenden Einfluss auf die gemessenen Hämoglobin-Adduktspiegel [72].…”

Section: Gst-polymorphismen Interindividuelle Unterschiede In Der Kounclassified

Acrylamid und Human-Biomonitoring

Umweltbundesamtes¹

2008

Bundesgesundheitsbl.

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Chromosome aberrations in tunnel workers exposed to acrylamide and N-methylolacrylamide

Cited by 24 publications

References 27 publications

In vivo Role of Cytochrome P450 2E1 and Glutathione-S-Transferase Activity for Acrylamide Toxicokinetics in Humans

In vivo Role of Cytochrome P450 2E1 and Glutathione-S-Transferase Activity for Acrylamide Toxicokinetics in Humans

Self-reported symptoms and neuropsychological function among tunnel workers previously exposed to acrylamide and N-methylolacrylamide

Acrylamid und Human-Biomonitoring

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Chromosome aberrations in tunnel workers exposed to acrylamide and N-methylolacrylamide

Cited by 24 publications

References 27 publications

In vivo Role of Cytochrome P450 2E1 and Glutathione-S-Transferase Activity for Acrylamide Toxicokinetics in Humans

In vivo Role of Cytochrome P450 2E1 and Glutathione-S-Transferase Activity for Acrylamide Toxicokinetics in Humans

Self-reported symptoms and neuropsychological function among tunnel workers previously exposed to acrylamide and N-methylolacryl­amide

Acrylamid und Human-Biomonitoring

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Self-reported symptoms and neuropsychological function among tunnel workers previously exposed to acrylamide and N-methylolacrylamide