Absence of acrylamide-induced genotoxicity in CYP2E1-null mice: Evidence consistent with a glycidamide-mediated effect
ABSTRACT Acrylamide, an animal carcinogen and germ cell mutagen present at low (ppm) levels in heated carbohydrate-containing foodstuffs, is oxidized by cytochrome P4502E1 (CYP2E1) to the epoxide glycidamide, which is believed to be responsible for the mutagenic and carcinogenic activity of acrylamide. We recently reported a comparison of the effects of acrylamide on the genetic integrity of germ cells of male wild-type and CYP2E1-null mice [B.I. Ghanayem, K.L. Witt, L. El-Hadri, U. Hoffler, G.E. Kissling, M.D. Shelby, J.B. Bishop, Comparison of germ-cell mutagenicity in male CYP2E1-null and wild-type mice treated with acrylamide: evidence supporting a glycidamide-mediated effect, Biol. Reprod. 72 (2005) 157-163]. In those experiments, dose-related increases in dominant lethal mutations were detected in uterine contents of female mice mated to acrylamide-treated wild-type males but not CYP2E1-null males, clearly implicating CYP2E1-mediated formation of glycidamide in the induction of genetic damage in male germ cells. We hypothesized that acrylamide-induced somatic cell damage is also caused by glycidamide. Therefore, to examine this hypothesis, female wild-type and CYP2E1-null mice were administered acrylamide (0, 25, 50mg/kg) by intraperitoneal injection once daily for 5 consecutive days. Twenty-four hours after the final treatment, blood and tissue samples were collected. Erythrocyte micronucleus frequencies were determined using flow cytometry and DNA damage was assessed in leukocytes, liver, and lung using the alkaline (pH>13) single cell gel electrophoresis (Comet) assay. Results were consistent with the earlier observations in male germ cells: significant dose-related increases in micronucleated erythrocytes and DNA damage in somatic cells were induced in acrylamide-treated wild-type but not in the CYP2E1-null mice. These results support the hypothesis that genetic damage in somatic and germ cells of mice-treated with acrylamide is dependent upon metabolism of the parent compound by CYP2E1. This dependency on metabolism has implications for the assessment of human risks resulting from occupational or dietary exposure to acrylamide. CYP2E1 polymorphisms and variability in CYP2E1 activity associated with, for example, diabetes, obesity, starvation, and alcohol consumption, may result in altered metabolic efficiencies leading to differential susceptibilities to acrylamide toxicities in humans.
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ABSTRACT: Background: Acrylamide (AA) is an important industrial chemical primarily. AA is also found in carbohydrate-rich foods that are prepared at high temperatures, such as French fries and potato chips. It is demonstrated that AA is a carcinogen and reproductive toxin and has ability to induce sperm damage. Objective: The aim of this study was to observe the effects of AA on sperm parameters and evaluation of sperm chromatin quality and testosterone hormone in mice. Materials and Methods: Totally, 16 adult male mice were divided into two groups. Mice of group A fed on basal diet; group B received basal diet and AA (10 mg/kg, water solution) for 35 days. The right cauda epididymis was incised and then placed in Ham’s F10 culture media at 37oC for 15 min. Released spermatozoa were used to analyze count, motility, morphology and viability. To determine the sperm DNA integrity and chromatin condensation, the cytochemical techniques including Aniline blue, Acridine orange and Chromomycin A3 staining were used. Results: AA-treated mice had poor parameters in comparison with control animals. In sperm chromatin assessments, except TB (p=0.16), significant differences were found in all of the tests between two groups. It was also seen a significant decrease in concentration of blood testosterone in AA-treated animals when compared to controls (p<0.001). Conclusion: According to our results, AA can affect sperm parameters as well as sperm chromatin condensation and DNA integrity in mice. These abnormalities may be related to the reduction in blood testosterone.Iranian Journal of Reproductive Medicine 05/2014; 12(5):335-42. · 0.19 Impact Factor
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ABSTRACT: Acrylamide is formed in heat processing of many common foods. According to animal cancer tests acrylamide is a carcinogen. To estimate the cancer risk from exposure via food, the response at high doses in the cancer tests with rats has to be extrapolated to the exposure levels in humans. Acrylamide is biotransformed to the epoxide glycidamide, which is assumed to be the cancer-risk increasing agent. Therefore in vivo doses of both acrylamide and glycidamide should be measured in rats and humans and related to the acrylamide intake. In vivo doses (area under the time-concentration curve, AUC) of reactive compounds can be determined from measured reaction products, adducts, to hemoglobin (Hb). A study in mice showed that the food matrix does not have an influence on the absorbed amount of acrylamide from food. There was a linear dose-response of Hb-adduct levels from acrylamide and glycidamide.
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ABSTRACT: Cancer remains the second leading cause of death in the United States, and the number of cases is expected to continue to rise worldwide. Cancer prevention strategies are crucial for reducing the cancer burden. The carcinogenic potential of dietary acrylamide exposure from cooked foods is unknown. Acrylamide is a by-product of the common Maillard reaction where reducing sugars (i.e., fructose and glucose) react with the amino acid, asparagine. Based on the evidence of acrylamide carcinogenicity in animals, the International Agency for Research on Cancer has classified acrylamide as a group 2A carcinogen for humans. Since the discovery of acrylamide in foods in 2002, a number of studies have explored its potential as a human carcinogen. This article outlines a systematic review of dietary acrylamide and human cancer, acrylamide exposure and internal dose, exposure assessment methods in the epidemiologic studies, existing data gaps, and future directions. A majority of the studies reported no statistically significant association between dietary acrylamide intake and various cancers, and few studies reported increased risk for renal, endometrial, and ovarian cancers; however, the exposure assessment has been inadequate leading to potential misclassification or underestimation of exposure. Future studies with improved dietary acrylamide exposure assessment are encouraged.Nutrition and Cancer 05/2014; 66(5). DOI:10.1080/01635581.2014.916323 · 2.47 Impact Factor