Rat two-generation reproduction and dominant lethal study of acrylamide in drinking water

Tyla, Rochelle W; Friedman, Marvin A.; Losco, Patricia E.; Fisher, L. C.; Johnson, Keith A.; Strother, Dale E.; Wolf, Claude H.

doi:10.1016/s0890-6238(00)00097-6

Cited by 82 publications

(51 citation statements)

References 21 publications

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“…Further studies have clearly indicated that DNA adduct formation in human spermatozoa has direct, negative impacts on fertility and is a good predictor of treatment outcome (Tyla et al, 2000). The current understanding of the molecular nature of the DNA damage is limited to mainly a handful of aryl/alkyl adducts (Witt and Bishop, 1996) and oxidative DNA modifications (De Iuliis et al, 2009).…”

Section: The Tunel Assaymentioning

confidence: 99%

The impact of sperm DNA damage in assisted conception and beyond: recent advances in diagnosis and treatment

Lewis

Aitken

Conner

et al. 2013

Reproductive BioMedicine Online

245

182

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Lewis, S.E.M. et al. (2013). The impact of sperm DNA damage in assisted conception and beyond: recent advances in diagnosis and treatment. Astract:Sperm DNA damage is a useful biomarker for male infertility diagnosis and prediction of assisted reproduction outcomes. It is associated with reduced fertilization rates, embryo quality and pregnancy rates, and higher rates of spontaneous miscarriage and childhood diseases. This review provides a synopsis of the most recent studies from each of the authors, all of whom have major track records in the field of sperm DNA damage in the clinical setting. It explores current laboratory tests and the accumulating body of knowledge concerning the relationship between sperm DNA damage and clinical outcomes. The paper proceeds to discuss the strengths, weaknesses and clinical applicability of current sperm DNA tests. Next, the biological significance of DNA damage in the male germ line is considered. Finally, as sperm DNA damage is often the result of oxidative stress in the male reproductive tract, the potential contribution of antioxidant therapy in the clinical management of this condition is discussed. DNA damage in human spermatozoa is an important attribute of semen quality. It should be part of the clinical work up and properly controlled trials addressing the effectiveness of antioxidant therapy should be undertaken as a matter of urgency. IntroductionMale factor infertility is implicated in more than 40% of couples presenting for assisted reproduction treatment. Conventional semen analysis continues to be the only routine test to diagnose this condition even though it is known that such descriptive assessments cannot discriminate between the spermatozoa of fertile and infertile men (Guzick et al., 2001). The shifting values for normality (all 'normal' values now lower) in the fifth edition of the WHO manual (World Health Organization, 2010) compared with the previous WHO editions may result in even less men being classified as infertile (Murray et al., 2012).

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Section: The Tunel Assaymentioning

confidence: 99%

The impact of sperm DNA damage in assisted conception and beyond: recent advances in diagnosis and treatment

Lewis

Aitken

Conner

et al. 2013

Reproductive BioMedicine Online

245

182

View full text Add to dashboard Cite

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“…Carcinogenicity studies in rats indicate that chronic acrylamide exposure increased the incidence of various tumor types (3,5,29) from the dose of 0.5 mg/kg/d, which would correspond to a human equivalent dose of 7.6 Ag/kg/d (29). Based on rodent studies, the cancer risk for humans through the dietary acrylamide was estimated to be 0.3 Â 10 À3 to 2.4 Â 10 À3 by lifetime acrylamide uptake of 70 Ag/d with f8-fold range of estimates driven by different cancer potency values and extrapolation models (6,7,13).…”

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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“…Der NOAEL für die systemische Neurotoxizität wird mit 500 μg/kg Körperge-wicht und Tag angegeben [34].…”

Section: Toxikologieunclassified

Acrylamid und Human-Biomonitoring

Umweltbundesamtes¹

2008

Bundesgesundheitsbl.

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Rat two-generation reproduction and dominant lethal study of acrylamide in drinking water

Cited by 82 publications

References 21 publications

The impact of sperm DNA damage in assisted conception and beyond: recent advances in diagnosis and treatment

The impact of sperm DNA damage in assisted conception and beyond: recent advances in diagnosis and treatment

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

Acrylamid und Human-Biomonitoring

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