Products Cited in Publications Worldwide Metabolism and genotoxicity of 4, 4'-oxydianiline is dependent on N-acetyltransferase 2 genetic polymorphism

Metabolism and genotoxicity of 4, 4'-oxydianiline is dependent on N-acetyltransferase 2 genetic polymorphism

Salazar-González, Raul A; Wise, James TF; Doll, Mark A; Hein, David W

DOI: PMID:

Abstract

4,4'-oxydianiline (ODA) is an environmental aromatic amine reasonably anticipated to be a human carcinogen. We investigated ODA genotoxicity and oxidative stress modified by N-acetyltransferase 2 (NAT2) genetic polymorphism in yeast and DNA repair deficient (UV5) Chinese hamster ovary cells (CHO) expressing human NAT2*4 (rapid acetylator allele) or human NAT2*5B (slow acetylator allele) and in cryopreserved human hepatocytes from rapid, intermediate, or slow NAT2 acetylator genotypes. N-acetylation of ODA was both concentration- and time-dependent and significantly higher in yeast and CHO cells expressing NAT2*4 versus NAT2*5B. ODA-induced DNA damage response and reactive oxygen species (ROS/RNS) were significantly higher, while intracellular reduced glutathione (GSH) and oxidized glutathione (GSSG) ratio or mitochondrial integrity were significantly lower in CHO cells expressing NAT2*4 than NAT2*5B. Dose- and NAT2 phenotype-dependent responses also were observed in human cryopreserved human hepatocytes. Our findings have important implications for precise risk assessments following exposures to ODA and azo dye precursors.

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A722543101-80-498%

4,4-Oxydianiline

48.0/100g

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N-(4-(4-Aminophenoxy)phenyl)acetamide

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