Segerbäck D, Calleman C J, Schroeder J L, Costa L G, Faustman E M
Center for Nutrition and Toxicology, Karolinska Institute, Novum, Huddinge, Sweden.
Carcinogenesis. 1995 May;16(5):1161-5. doi: 10.1093/carcin/16.5.1161.
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.
丙烯酰胺是一种烷基化剂，它与DNA的直接反应非常缓慢，在艾姆斯试验中呈阴性，但对小鼠和大鼠具有致癌性。为了解释丙烯酰胺的致癌起始特性，我们研究了在体外利用代谢系统以及在体内给小鼠和大鼠腹腔注射14C标记的丙烯酰胺后DNA加合物的形成情况。在这两个物种中发现的一种主要加合物是N-7-(2-氨基甲酰基-2-羟基-乙基)鸟嘌呤，它是由DNA与环氧化物代谢产物缩水甘油酰胺反应形成的。这种加合物在两种啮齿动物物种的不同器官中的水平相似，这支持了以下观点：缩水甘油酰胺在组织中相对均匀地分布，并且丙烯酰胺致癌作用中的器官特异性不能通过DNA反应性代谢产物在靶器官中的选择性积累来解释。
