Powell Jeannine H, Gannett Peter M
Department of Basic Pharmaceutical Sciences, School of Pharmacy, West Virginia University, Morgantown 26506-9530, USA.
J Environ Pathol Toxicol Oncol. 2002;21(1):1-31.
Aryl hydrazines carcinogenesis has been studied for over 25 years and remains poorly understood, although most aryl hydrazines are toxic, tumorigenic, or carcinogenic. In this article, aryl hydrazine carcinogenesis is reviewed comprehensively. The relevant chemistry and biochemistry of aryl hydrazines are first addressed and provide the framework for understanding how aryl hydrazines are metabolized, the reactive intermediates that are produced, and the biological reactive intermediates and products that are formed. Issues of DNA damage, mutagenicity, and enzyme activation are next addressed followed by a brief review of aryl hydrazine tumorigenicity studies. Because several related substrates are metabolized to the same intermediates as are aryl hydrazines, they are briefly discussed. The review concludes with a short discussion of the possible mechanism of carcinogenesis by aryl hydrazines.
芳基肼类的致癌作用已被研究了25年多，但仍未被充分理解，尽管大多数芳基肼类具有毒性、致瘤性或致癌性。本文对芳基肼类的致癌作用进行了全面综述。首先阐述了芳基肼类的相关化学和生物化学知识，为理解芳基肼类如何代谢、产生的反应性中间体以及形成的生物反应性中间体和产物提供了框架。接着讨论了DNA损伤、致突变性和酶激活等问题，随后简要回顾了芳基肼类的致瘤性研究。由于几种相关底物与芳基肼类代谢生成相同的中间体，因此也对它们进行了简要讨论。综述最后简短讨论了芳基肼类可能的致癌机制。
