Acrylamide is metabolized to glycidamide in the rat: evidence from hemoglobin adduct formation

Calleman, Carl Johan; Bergmark, Emma; Costa, Lucio G.

doi:10.1021/tx00017a004

Cited by 152 publications

(70 citation statements)

References 26 publications

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“…We observed gender differences in the glycidamideto-acrylamide adduct ratio, with women having higher ratios than men, which is consistent with previous findings from animal studies (36). Acrylamide is metabolized to glycidamide mainly through the action of CYP2E1 (37)(38)(39), which is affected by genetic factors (40)(41)(42) and other exposures such as ethanol and smoking (43,44). Because the magnitude of these factors could be different in each individual, a high intersubject variability in the glycidamide-to-acrylamide adduct ratio is expected and was observed in our study.…”

Section: Discussionsupporting

confidence: 91%

Assessment of the Relation between Biomarkers for Smoking and Biomarkers for Acrylamide Exposure in Humans

Vesper

Bernert

Ospina

et al. 2007

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Smoking is an important source of acrylamide exposure in the general population. We assessed the relationship between hemoglobin adducts of acrylamide (HbAA) and glycidamide (HbGA) as biomarkers of acrylamide exposure and plasma cotinine (PC) as biomarkers of tobacco smoke exposure in 94 men and 67 women. The median (5th-95th percentile) biomarker concentrations (pmol/g Hb) in the group of individuals with PC concentrations of V10 ng/mL were 51 (29-155) and 34 (16-117) for HbAA and HbGA, respectively. They were significantly lower than those in the group of individuals with PC concentrations of >10 ng/mL [194 (87-403) and 107 (41-215) for HbAA and HbGA, respectively]. In individuals with PC concentrations of <1 ng/mL, HbAA and HbGA were similar to those observed in the group with PC values of V10 ng/mL. The intersubject variability was profoundly smaller in the group with PC values of V10 ng/mL compared with the group with PC values of >10 ng/mL. Although HbAA and HbGA could be categorized into distinguishable groups using PC concentration ranges commonly used to categorize presumed smokers and nonsmokers, no significant relationship was observed between these two biomarkers and PC within each group. The different exposure periods reflected by these biomarkers and the resulting different susceptibility to short-term variations in exposure patterns may in part explain these observations. The findings suggest that tobacco smoke exposure in individuals with PC values of <1 ng/mL has only a minimal effect

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Section: Discussionsupporting

confidence: 91%

Assessment of the Relation between Biomarkers for Smoking and Biomarkers for Acrylamide Exposure in Humans

Vesper

Bernert

Ospina

et al. 2007

Cancer Epidemiology, Biomarkers &Amp; Prevention

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“…Catabolism of both acrylamide and glycidamide takes place in such a manner that glutathione-dependent GST enzyme is catalyzed and excreted from the body via urination. The main excretion metabolite of acrylamide is the structure of N-acetyl-S-(3-Amino-3-oxopropyl)-cysteine (65,66). In our study, GSH was used in the cells for detoxifying the acrylamide in both digestive system and liver when we administered acrylamide, and a signifi cant decrease was experienced in GSH levels of the tissues.…”

Section: Discussionmentioning

confidence: 73%

The protective effect of N-acetylcysteine against acrylamide toxicity in liver and small and large intestine tissues

Altınöz¹,

Türköz²,

Vardı³

2015

BLL

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Abstract:The aim of this study was to investigate the protective effects of N-acetylcysteine against acrylamide toxicity in liver and small and large intestine tissues in rats. The rats were divided into four groups. Acrylamide administration increased MDA levels in all tissues significantly (p < 0.05). But acrylamide+NAC administration decreased MDA levels signifi cantly as compared to the acrylamide group, and lowered it to a level close to the control group values (p < 0.05). GSH levels in liver and small intestine tissues reduced signifi cantly in the acrylamide group (p < 0.05). But acrylamide+NAC administration increased GSH levels signifi cantly in all tissues. Whereas GST activity decreased signifi cantly in the acrylamide group in liver and small intestine tissues as compared to the other groups (p < 0.05), the GST activity increased signifi cantly in the acrylamide+NAC group in all tissues as compared to the acrylamide group (p < 0.05). Liver histopathology showed that the liver epithelial cells were damaged signifi cantly in the acrylamide group. Small intestine histopathology showed that the intestinal villous epithelial cells were damaged signifi cantly in the acrylamide group. Our results indicate that a high level of acrylamide causes oxidative damage in liver and small and large intestine tissues, while N-acetylcysteine administration in a pharmacological dose shows to have an antioxidant effect in preventing this damage (Tab. 2, Fig. 2, Ref. 66). Text in PDF www.elis.sk.

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“…In vitro testing of acrylamide in Chinese Hamster ovary (CHO) and mouse lymphoma (MOLY) L5178Y Tk +/− assays indicates that acrylamide is a clastogen (28). Acrylamide is oxidized by cytochrome P450 2E1 (CYP2E1) to the reactive epoxide glycidamide that is hypothesized to be responsible for the genotoxic and carcinogenic activity of acrylamide in mice (29)(30)(31)(32). However, the situation is less clear for rats and humans, that produce less glycidamide than mice at equivalent exposure levels (33).…”

Section: Introductionmentioning

confidence: 99%

Differential genotoxicity of acrylamide in the micronucleus andPig-a gene mutation assays in F344 rats and B6C3F1 mice

Hobbs¹,

Davis²,

Shepard³

et al. 2016

MUTAGE

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Acrylamide is used in many industrial processes and is present in a variety of fried and baked foods. In rodent carcinogenicity assays, acrylamide exposure leads to tumour formation at doses lower than those demonstrated to induce genotoxic damage. We evaluated the potential of acrylamide to induce structural DNA damage and gene mutations in rodents using highly sensitive flow cytometric analysis of micronucleus and Pig-a mutant frequencies, respectively. Male F344 rats and B6C3F1 mice were administered acrylamide in drinking water for 30 days at doses spanning and exceeding the range of acrylamide exposure tested in cancer bioassays-top dose of 12.0 and 24.0 mg/kg/day in mice and in rats, respectively. A positive control, N-ethyl-N-nitrosourea, was administered at the beginning and end of the study to meet the expression time for the two DNA damage phenotypes. The results of the micronucleus and Pig-a assays were negative and equivocal, respectively, for male rats exposed to acrylamide at the concentrations tested. In contrast, acrylamide induced a dose-dependent increase in micronucleus formation but tested negative in the Pig-a assay in mice. Higher plasma concentrations of glycidamide in mice than rats are hypothesized to explain, at least in part, the differences in the response. Benchmark dose modelling indicates that structural DNA damage as opposed to point mutations is most relevant to the genotoxic mode of action of acrylamide-induced carcinogenicity. Moreover, the lack of genotoxicity detected at <6.0 mg/kg/day is consistent with the notion that non-genotoxic mechanisms contribute to acrylamide-induced carcinogenicity in rodents.

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Acrylamide is metabolized to glycidamide in the rat: evidence from hemoglobin adduct formation

Cited by 152 publications

References 26 publications

Assessment of the Relation between Biomarkers for Smoking and Biomarkers for Acrylamide Exposure in Humans

Assessment of the Relation between Biomarkers for Smoking and Biomarkers for Acrylamide Exposure in Humans

The protective effect of N-acetylcysteine against acrylamide toxicity in liver and small and large intestine tissues

Differential genotoxicity of acrylamide in the micronucleus andPig-a gene mutation assays in F344 rats and B6C3F1 mice

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