Influence of heredity on human sensitivity to environmental chemicals.
Influence of heredity on human sensitivity to environmental chemicals.
复制标题
遗传对人类对环境化学物质敏感性的影响。
DOI：
10.1002/em.2850250614
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发表时间：
1995
影响因子：
2.8
通讯作者：
Weber,WW
中科院分区：
文献类型：
--
作者：
Weber,WW
个体对环境化学物质反应的遗传特征在人群中很常见。谷胱甘肽S-转移酶、CYP1A2、N-乙酰转移酶和对氧磷酶的遗传变异例证了代谢变异与个体对癌症和其他环境来源毒物的易感性之间的关系。遗传性受体蛋白变体是具有巨大药物遗传学潜力的蛋白质的子集，迄今为止尚未从药物遗传学的角度进行广泛的探索。所考虑的感兴趣的例子包括与急性早幼粒细胞白血病中的视黄酸耐药性相关的受体变异、与前列腺癌中对抗雄激素的矛盾反应以及与色素性视网膜炎相关的受体变异。还讨论了其他具有药物遗传学意义的可遗传蛋白质变异，这些变异会导致抗生素引起的耳聋、糖皮质激素可治疗的醛固酮增多症和高血压、长QT综合征和铍引起的肺部疾病。这些特征表明，对变异反应的分子基础和机制的了解如何有助于敏感人群的预防，以及改善对环境化学物质引起的遗传性疾病的治疗。 © 1995 Wiley-Liss, Inc.
Hereditary peculiarities in individual responses to environmental chemicals are a common occurrence in human populations. Genetic variation in glutathi‐one S‐transferase, CYP1A2, N‐acetyltransferase, and paraoxonase exemplify the relationship of metabolic variation to individual susceptibility to cancer and other toxicants of environmental origin. Heritable receptor protein variants, a subset of proteins of enormous pharmacogenetic potential that have not thus far been extensively explored from the pharmacogenetic standpoint, are also considered. Examples of interest that are considered include receptor variants associated with retinoic acid resistance in acute promyelocytic leukemia, with paradoxical responses to antiandrogens in prostate cancer, and with retinitis pigmentosa. Additional heritable protein variants of pharmacogenetic interest that result in antibiotic‐induced deafness, glucocorticoid‐reme‐diable aldosteronism and hypertension, the long‐QT syndrome, and beryllium‐induced lung disease are also discussed. These traits demonstrate how knowledge of the molecular basis and mechanism of the variant response may contribute to its prevention in sensitive persons as well as to improved therapy for genetically conditioned disorders that arise from environmental chemicals. © 1995 Wiley‐Liss, Inc.