3,5-dimethylaniline-induced mutagenesis in Chinese hamster ovary cells
expressing human cytochrome P450 1A2 and sulfotransferase
Laboratory, Faculty of Biotechnology (Biomaterials), College of Applied Life
Science, SARI, Jeju National University, Jeju, 63243, Republic of Korea
*Corresponding Author Email : email@example.com
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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