Citation

Kong W, Kuester RK, Gallegos A, Sipes IG. Toxicology 2011; 290(2-3): 271-277.

Affiliation

Department of Pharmacology, College of Medicine, The University of Arizona, Tucson, AZ 85724, United States.

Copyright

(Copyright © 2011, Elsevier Publishing)

DOI

10.1016/j.tox.2011.10.006

PMID

22019925

PMCID

PMC3248618

Abstract

2,2-Bis(bromomethyl)-1,3-propanediol (BMP) is an extensively used brominated flame retardant found in urethane foams and polyester resins. In a 2-year dietary study conducted by the National Toxicology Program, BMP caused neoplastic lesions at multiple sites including the urinary bladder in both rats and mice. The mechanism of its carcinogenic effect is unknown. In the present study, using SV-40 immortalized human urothelial cells (UROtsa), endpoints associated with BMP induced DNA damage and oxidative stress were investigated. The effects of time (1-24h) and concentration (5-100μM) on BMP induced DNA strand breaks were assessed via the alkaline comet assay. The results revealed evidence of DNA strand breaks at 1 and 3h following incubation of cells with non-cytotoxic concentrations of BMP. Strand breaks were not present after 6h of incubation. Evidences for BMP associated oxidative stress include: an elevation of intracellular ROS formation as well as induction of Nrf2 and HSP70 protein levels. In addition, DNA strand breaks were attenuated when cells were pre-treated with N-acetyl-l-cysteine (NAC) and oxidative base modifications were revealed when a lesion specific endonuclease, human 8-hydroxyguanine DNA glycosylase 1 (hOGG1) was introduced into the comet assay. In conclusion, these results demonstrate that BMP induces DNA strand breaks and oxidative base damage in UROtsa cells. Oxidative stress is a significant, determinant factor in mediating these DNA lesions. These early genotoxic events may, in part, contribute to BMP-induced carcinogenesis observed in rodents.

Language: en