Influence of Persistent Contaminants and Steroid Hormones on Glioblastoma Cell Growth

Abstract

Glioblastoma multiforme (GBM), a malignancy characterized by its rapid progression, presents a lower risk of occurrence in women during their reproductive years. Necrosis of brain tissue during tumor invasion releases free lipids, and therefore might release contaminants stored in phospholipid-rich neuronal tissue. This study assesses the growth response of two human glioblastoma cell lines, T98G and U138-MG, treated with environmental chemicals known or likely to persist within the brain. Persistent chlorinated pesticides, industrial contaminants, persistant perfluorinated chemicals, and steroid hormones were assayed over a range of concentrations. Although cytotoxic effects were seen in both T98G and U138-MG cells, proliferative responses occurred only in the T98G cell line. Dichlorodiphenyltrichloroethane (DDT), dichlorodiphenyldichloroethylene (DDE), and polychlorinated biphenyl (PCB) 153 were cytotoxic in both lines at 5000 nM. Perfluorodecanoic acid (PFDA), perfluorooctane sulfonate (PFOS), and testosterone stimulated proliferation in the T98G cells at 500, 1000, and 1000 nM, respectively. However, a perfluorinated salt (ammonium perfluorooctanoate; C8) and a weak androgen (dihydroepiandrosterone; DHEA) did not affect relative cell number in this GBM line, suggesting the proliferative effect is not through the activation of an androgen receptor. Exposure to environmental chemicals that result in a mitogenic response may increase the rate of glioblastoma tumor growth and result in the development of more aggressive forms of GBM tumors.

Acknowledgements

The authors thank Chad Boustany, Desirae Templeton, Dr. Kristine Krajnak, and Dr. Kristine Willett for their help and technical support. This research was supported, in part, by the Department of Biology, West Virginia University, and the West Virginia University Research Corporation.