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Camptothecin Efficacy to Poison Top1 Is Altered by Bisphenol A in Mouse Embryonic Fibroblasts.

Authors :
Sonavane, Manoj
Sykora, Peter
Andrews, Joel F.
Sobol, Robert W.
Gassman, Natalie R.
Source :
Chemical Research in Toxicology. 6/18/2018, Vol. 31 Issue 6, p510-519. 10p.
Publication Year :
2018

Abstract

Bisphenol A (BPA) is used heavily in the production of polycarbonate plastics, thermal receipt paper, and epoxies. Ubiquitous exposure to BPA has been linked to obesity, diabetes, and breast and reproductive system cancers. Resistance to chemotherapeutic agents has also been shown in cancer cell models. Here, we investigated BPA's ability to confer resistance to camptothecin (CPT) in mouse embryonic fibroblasts (MEFs). MEFs are sensitive to CPT; however, co-exposure of BPA with CPT improved cell survival. Co-exposure significantly reduced Top1-DNA adducts, decreasing chromosomal aberrations and DNA strand break formation. This decrease occurs despite BPA treatment increasing the protein levels of Top1. By examining chromatin structure after BPA exposure, we determined that widespread compaction and loss of nuclear volume occurs. Therefore, BPA reduced CPT activity by reducing the accessibility of DNA to Top1, inhibiting DNA adduct formation, the generation of toxic DNA strand breaks, and improving cell survival. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
0893228X
Volume :
31
Issue :
6
Database :
Academic Search Index
Journal :
Chemical Research in Toxicology
Publication Type :
Academic Journal
Accession number :
130291236
Full Text :
https://doi.org/10.1021/acs.chemrestox.8b00050