Dobrovolsky Vasily N, Pacheco-Martinez M Monserrat, McDaniel L Patrice, Pearce Mason G, Ding Wei
Division of Genetic and Molecular Toxicology, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR, USA.
Departamento de Ciencias de la Salud, Universidad Autónoma Metropolitana Iztapalapa, Mexico City, Mexico.
Food Chem Toxicol. 2016 Jan;87:120-7. doi: 10.1016/j.fct.2015.12.006. Epub 2015 Dec 11.
Acrylamide (ACR) and glycidyl methacrylate (GMA) are structurally related compounds used for making polymers with various properties. Both chemicals can be present in food either as a byproduct of processing or a constituent of packaging. We performed a comprehensive evaluation of ACR and GMA genotoxicity in Fisher 344 rats using repeated gavage administrations. Clastogenicity was measured by scoring micronucleated (MN) erythrocytes from peripheral blood, DNA damage in liver, bone marrow and kidneys was measured using the Comet assay, and gene mutation was measured using the red blood cell (RBC) and reticulocyte Pig-a assay. A limited histopathology evaluation was performed in order to determine levels of cytotoxicity. Doses of up to 20 mg/kg/day of ACR and up to 250 mg/kg/day of GMA were used. ACR treatment resulted in DNA damage in the liver, but not in the bone marrow. While ACR was not a clastogen, it was a weak (equivocal) mutagen in the cells of bone marrow. GMA caused DNA damage in the cells of bone marrow, liver and kidney, and induced MN reticulocytes and Pig-a mutant RBCs in a dose-dependent manner. Collectively, our data suggest that both compounds are in vivo genotoxins, but the genotoxicity of ACR is tissue specific.
丙烯酰胺（ACR）和甲基丙烯酸缩水甘油酯（GMA）是结构相关的化合物，用于制造具有各种特性的聚合物。这两种化学物质在食品中既可以作为加工副产物存在，也可以作为包装成分存在。我们通过重复灌胃给药对Fisher 344大鼠的ACR和GMA遗传毒性进行了全面评估。通过对外周血中的微核（MN）红细胞进行评分来测量致断裂性，使用彗星试验测量肝脏、骨髓和肾脏中的DNA损伤，并使用红细胞（RBC）和网织红细胞Pig-a试验测量基因突变。为了确定细胞毒性水平，进行了有限的组织病理学评估。使用的ACR剂量高达20毫克/千克/天，GMA剂量高达250毫克/千克/天。ACR处理导致肝脏中的DNA损伤，但未导致骨髓中的DNA损伤。虽然ACR不是断裂剂，但它在骨髓细胞中是一种弱（不确定）诱变剂。GMA导致骨髓、肝脏和肾脏细胞中的DNA损伤，并以剂量依赖的方式诱导MN网织红细胞和Pig-a突变RBC。总体而言，我们的数据表明这两种化合物都是体内遗传毒素，但ACR的遗传毒性具有组织特异性。
