Combined Effects of High-Dose Bisphenol A and Oxidizing Agent (KBrO3) on Cellular Microenvironment, Gene Expression, and Chromatin Structure of Ku70-deficient Mouse Embryonic Fibroblasts

Published

April 15, 2016

Author(s)

Erdem Coskun, Pawel Jaruga, Miral M. Dizdar, Natalie Gassman, Samuel Wilson

Abstract

Background: Exposure to the environmental endocrine disrupting chemical bisphenol A (BPA) has been reported to alter global gene expression, induce epigenetic modifications, and interfere with the complex regulatory networks of cells. In addition to these reprogramming events, we have demonstrated that BPA exposure generates reactive oxygen species and promotes cellular survival when co-exposed with dietary oxidizing agent potassium bromate (KBrO3). Objectives: We aimed to determine the cellular microenvironment changes induced by BPA co-exposure that promoted cell survival and determine if these changes were unique to co-exposure. Methods: Ku70-deficient cells were exposed to BPA, KBrO3, and co-exposed with both agents. 4 h and 24 h post-damage initiation, we performed whole genome microarray analysis and evaluated chromatin structure, glutathione content, and intracellular pH. Results: We found that 4 h post-damage initiation BPA co-exposure suppressed DNA repair by condensing chromatin and reducing transcription of DNA repair proteins. BPA also stabilized the intracellular pH change observed after KBrO3 only treatment. 24 h post-damage initiation, BPA exposed cells showed less condensed chromatin; their intracellular glutathione was slightly depleted; intracellular pH was reduced, while KBrO3 alone showed an increase in pH; and significant up-regulation in DNA repair proteins was observed only for the co-exposure condition. Conclusion: These results support an induction of an adaptive response due to BPA co-exposure that results in the delayed repair of oxidatively induced DNA lesions. Further work is required to understand the long-term consequences of this delayed repair; however, this study demonstrates that BPA exposure significantly alters the cellular microenvironment to promote survival.

Citation

Environmental Health Perspectives

Volume

124

Issue

8

Pub Type

Journals

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DOI Link

Keywords

adaptive response, bisphenol A, DNA damage, DNA repair, endocrine disruptor, oxidative stress, oxidatively induced DNA lesions, potassium bromate

Citation

Coskun, E. , Jaruga, P. , Dizdar, M. , Gassman, N. and Wilson, S. (2016), Combined Effects of High-Dose Bisphenol A and Oxidizing Agent (KBrO3) on Cellular Microenvironment, Gene Expression, and Chromatin Structure of Ku70-deficient Mouse Embryonic Fibroblasts, Environmental Health Perspectives, [online], https://doi.org/10.1289/EHP237 (Accessed April 25, 2024)