Minchin R F, Kadlubar F F, Ilett K F
Department of Pharmacology, University of Western Australia, Nedlands.
Mutat Res. 1993 Nov;290(1):35-42. doi: 10.1016/0027-5107(93)90030-j.
Acetylator phenotype is a common genetic trait in humans as well as other mammals. It results from the presence of several mutations in one of the genes encoding for arylamine N-acetyltransferase. The polymorphism has been associated with several disease states including colorectal cancer. Several epidemiological studies suggest that rapid acetylators are more susceptible to colorectal cancer than slow acetylators. Moreover, individuals that are both rapid acetylators and exhibit a high cytochrome P450 1A2 activity appear to have an even higher risk of colorectal cancer. These observations not only suggest an interesting genetic link to non-familial colon cancer but also suggest that carcinogens that are activated by N-acetyltransferase and cytochrome P450 1A2 may contribute to the etiology of this disease. Heterocyclic amines present in cooked food such as "well done" red meat are carcinogenic in experimental animals forming tumours in several target tissues including the small intestines. We have shown that human polymorphic N-acetyltransferase is present in human colon tissue and that it is capable of activating several heterocyclic amine carcinogens present in cooked food. These studies provide good circumstantial evidence that rapid acetylators may be predisposed to colorectal cancer.
乙酰化表型是人类以及其他哺乳动物的一种常见遗传特征。它是由编码芳胺N - 乙酰基转移酶的基因之一中存在的几种突变导致的。这种多态性与包括结直肠癌在内的几种疾病状态有关。多项流行病学研究表明，快速乙酰化者比慢速乙酰化者更容易患结直肠癌。此外，既是快速乙酰化者又表现出高细胞色素P450 1A2活性的个体似乎患结直肠癌的风险更高。这些观察结果不仅表明与非家族性结肠癌存在有趣的遗传联系，还表明由N - 乙酰基转移酶和细胞色素P450 1A2激活的致癌物可能与这种疾病的病因有关。熟食中存在的杂环胺，如“熟透”的红肉中的杂环胺，在实验动物中具有致癌性，会在包括小肠在内的多个靶组织中形成肿瘤。我们已经表明，人类多态性N - 乙酰基转移酶存在于人类结肠组织中，并且它能够激活熟食中存在的几种杂环胺致癌物。这些研究提供了充分的间接证据，表明快速乙酰化者可能易患结直肠癌。
