Mechanisms of carcinogenicity of aryl hydrazines, aryl hydrazides, and arenediazonium ions

Abstract

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.