Formation of N-7-(2-carbamoyl-2-hydroxyethyl)guanine in DNA of the mouse and the rat following intraperitoneal administration of [14C]acrylamide

University of Washington Seattle, Seattle, Washington, United States
Carcinogenesis (Impact Factor: 5.27). 06/1995; 16(5):1161-5. DOI: 10.1093/carcin/16.5.1161
Source: PubMed

ABSTRACT Acrylamide is an alkylating agent which reacts very slowly in direct reactions with DNA and is negative in the Ames test, but is carcinogenic in mice and rats. In order to explain the cancer-initiating properties of acrylamide we have studied DNA adduct formation in vitro with a metabolizing system and in vivo in mice and rats following i.p. administration of 14C-labeled acrylamide. A major adduct found in both species was N-7-(2-carbamoyl-2-hydroxy-ethyl)guanine, formed by reaction of the DNA with the epoxide metabolite glycidamide. The levels of this adduct were similar in the different organs of the two rodent species, which supports the notion that glycidamide is relatively evenly distributed among tissues and that the organ-specificity in acrylamide carcinogenesis cannot be explained by a selective accumulation of the DNA-reactive metabolite in target organs.

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    • "AA is a neurotoxic agent to humans (Hagmar et al., 2001), and is classified as a probable carcinogen to human (Group 2A) by the International Agency for Research on Cancer (IARC, 1994). Both AA and its epoxy-metabolite, glycidamide (GA) are reactive towards biomacromolecules and are suspected to cause genotoxicity (Paulsson et al., 2003; Segerbäck et al., 1995). Several epidemiological studies have suggested its associations with various cancer risks, e.g., breast cancer (Olesen et al., 2008), renal cancer (Hogervorst et al., 2008), and lung cancer (Hogervorst et al., 2009), while a number of studies have shown no significant association with cancers of bowel, kidney, bladder, oral, esophageal, laryngeal, breast, ovary, or prostate (Mucci et al., 2003; Pelucchi et al., 2006). "
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    ABSTRACT: Acrylamide (AA), a probable human carcinogen, is present in high-temperature-processed foods, and has frequently been detected in humans worldwide. In the present study, the levels of a major AA metabolite, N-acetyl-S-(2-carbamoylethyl)-cysteine (AAMA) were measured in urine samples collected in two separate events with 3d interval from Korean children (n=31, 10-13years old), and their diets were surveyed for 4d period prior to the second urine sampling. Daily AA intake was estimated from AAMA urinary levels and the influence of food consumption on urinary AAMA levels was investigated. The concentrations of metabolite AAMA in urine ranged between 15.4 and 196.3ng/mL, with a median level of 68.1ng/mL, and the levels varied by day considerably even in a given child. Children who were exposed to environmental smoke at home exhibited significantly higher levels of AAMA in urine, suggesting the importance of passive smoking as a source of AA exposure among children. Median (95th percentile) values of daily AA intake in Korean children were 1.04 (2.47)μg/kgbodyweight/day, which is higher than those reported elsewhere. After adjustment for gender, body mass index, and smoking status of family members, the consumptions of cracker and chocolate were identified to be significantly associated with the concentrations of AAMA in urine. The result of this study will provide information useful for developing public health and safety management for AA.
    Science of The Total Environment 04/2013; 456-457C:17-23. DOI:10.1016/j.scitotenv.2013.03.057 · 4.10 Impact Factor
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    • "[1] [2] [3] It is evidentially thought to be a neurotoxicant, carcinogen and terratogen in animals. [1] [4] [5] Neurotoxic effects in humans have been observed at high levels of exposure in occupational settings. Acrylamide is oxidized to the epoxide glycidamide via an enzymatic reaction involving cytochrome P450 2E1. "
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    ABSTRACT: Worldwide contamination by acrylamide, a neurotoxicant and carcinogen in animals, is becoming a significant problem. We isolated three novel acrylamide-degrading bacteria from domestic wastewater in Chonburi, Thailand. Using biochemical characteristics and 16S rRNA gene sequencing, the strains were identified as Klebsiella pneumoniae, Kluyvera georgiana and Enterococcus faecalis. K. georgiana strain No. 2 was selected for further characterization due to its degradation potential of high concentrations of acrylamide at the mesophilic temperatures. The strain grew well in the presence of acrylamide at concentrations to 0.5 % (w/v), pH 5.0 to 7.0 and 37°C. Degradation of acrylamide to acrylic acid began after 30 min of cultivation as a biomass-dependent manner. Mass balance analysis revealed 92.3 % conversion of acrylamide to acrylic acid and two lower polarity compounds. Strain No. 2 degraded many aliphatic amides but not iodoacetamide and thioacetamide. High degradation level (>80 %) was found with propionamide, cyanoacetamide and acetamide. Moderate degradation was obtained in the order of formamide > butyramide > lactamide > urea while sodium azide provided 34 % degradation. These findings render this novel bacterium attractive for biodegradation of acrylamide and other aliphatic amides in the environment.
    Journal of Environmental Science and Health Part A Toxic/Hazardous Substances & Environmental Engineering 09/2012; 47(11):1491-9. DOI:10.1080/10934529.2012.680312 · 1.14 Impact Factor
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    • "Acrylamide (CH 2 =CHCONH 2 ) is an important monomer used as a conjugated reactive molecule in polyacrylamide production as well as a binding, thickening, or flocculating agent in industrial applications (Prabu and Thatheyus, 2007; Prasad, 1982; Wampler and Ensign, 2005). It is also a neurotoxicant, carcinogen and terratogen in animals (Cherry et al., 1956; IARC, 1994; Prabu and Thatheyus, 2007; Segerbäck et al., 1995; Tilson and Cabe, 1979). Neurotoxic effects in humans have been observed at high levels of exposure in occupational settings. "
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    ABSTRACT: A widespread use of acrylamide, probably a neurotoxicant and carcinogen, in various industrial processes has led to environmental contamination. Fortunately, some microorganisms are able to derive energy from acrylamide. In the present work, we reported the isolation and characterization of a novel acrylamide-degrading bacterium from domestic wastewater in Chonburi, Thailand. The strain grew well in the presence of acrylamide as 0.5% (W/V), at pH 6.0 to 9.0 and 25 degrees C. Identification based on biochemical characteristics and 16S rRNA gene sequence identified the strain as Enterobacter aerogenes. Degradation of acrylamide to acrylic acid started in the late logarithmic growth phase as a biomass-dependent pattern. Specificity of cell-free supernatant towards amides completely degraded butyramide and urea and 86% of lactamide. Moderate degradation took place in other amides with that by formamide > benzamide > acetamide > cyanoacetamide > propionamide. No degradation was detected in the reactions of N,N-methylene bisacrylamide, sodium azide, thioacetamide, and iodoacetamide. These results highlighted the potential of this bacterium in the cleanup of acrylamide/amide in the environment.
    Journal of Environmental Sciences 03/2011; 23(3):396-403. DOI:10.1016/S1001-0742(10)60422-6 · 1.92 Impact Factor
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