Journal of Environmental Biology

2,6-and 3,5-dimethylaniline-induced mutagenesis in Chinese hamster ovary cells expressing human cytochrome P450 1A2 and sulfotransferase

M.Y. Kim* 

Toxicology Laboratory, Faculty of Biotechnology (Biomaterials), College of Applied Life Science, SARI, Jeju National University, Jeju, 63243, Republic of Korea

*Corresponding Author Email : jeffmkim@jejunu.ac.kr

Paper received: 09.09.2019??????? ?????????????????????????????????????? Revised received: 14.12.2019????????????? ??????????????????????? Accepted: 13.01.2020

Abstract

Aim: The aim of this study was to test the hypothesis that human cytochrome P450 1A2 (CYP1A2) and sulfotransferase (SULT) contribute to the phase I and II bioactivation of 2,6-dimethylaniline (2,6-DMA) and 3,5-dimethylaniline (3,5-DMA) in affecting the incidence of genotoxicity.

Methodology: 5P3H1 cells carrying cytochrome P450 1A2 (CYP1A2) and SULT cells were treated with various concentrations of 2,6-and 3,5-DMA for 48 hr or their N-hydroxyl and aminophenol metabolites for 1 hr in the absence or presence of 2,6-Dichloro-4-nitrophenol (DCNP). Cell lethality was assayed by trypan blue exclusion and induced mutagenesis of adenine phosphoribosyl transferase (aprt) gene was also evaluated.          

Results: A significant dose-dependent increase in cytotoxicity and mutant fraction was observed after treatment with 2,6- and 3,5-DMA, and their metabolites; N-hydroxy and aminophenol metabolites are more potent than the parent compounds. Addition of sulfotransferase inhibitor DCNP decreased the cytotoxic and mutagenic effects of 2,6- and 3,5-DMA, and their metabolites in a dose-dependent manner.     

Interpretation: This research indicate that 2,6 and 3,5-DMA are mutagenic, and their toxicity in model systems depend on metabolic activation. This activation is mediated by CYP1A2 and SULT enzymes.    

Key words: Chinese hamster, Cytochrome, Dimethylaniline, Ovary cells, Sulfotransferase

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