Comparison of 2,2-bis(bromomethyl)-1,3-propanediol induced genotoxicity in UROtsa cells and primary rat hepatocytes: relevance of metabolism and oxidative stress.

Weixi Kong, Pengfei Gu, Gabriel A Knudsen, I Glenn Sipes

Index: Toxicol. Lett. 222(3) , 273-9, (2013)

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Abstract

2,2-Bis(bromomethyl)-1,3-propanediol (BMP) is a brominated flame retardant used in urethane foams and polyester resins. In a two year dietary study, BMP caused neoplastic lesions at multiple sites including the urinary bladder of both rats and mice. However, liver was not a target tissue. We previously reported that BMP elicited oxidative DNA damage in a human uroepithelial cell line (UROtsa). The present in vitro study investigated the susceptibility of target (UROtsa cells) and non-target cells (primary rat hepatocytes) to BMP-induced genotoxicity. In contrast to hepatocytes, BMP exhibited greater genotoxic potential in UROtsa cells as evidenced by the concentration dependent increase in DNA strand breaks and DNA binding. Total content of intracellular GSH quantified in UROtsa cells (2.7±1.0nmol/mg protein) was 4 fold lower than that in hepatocytes (10.7±0.3nmol/mg protein). HPLC analysis indicated BMP was not metabolized and/or consumed in UROtsa cells at any of the concentrations tested (10-250μM) but was extensively converted to a mono-glucuronide in hepatocytes. These results demonstrate that a target cell line such as UROtsa cells are more susceptible to BMP-induced DNA damage when compared to non-target cells. This increased susceptibility may relate to the deficiency of antioxidant and/or metabolic capabilities in UROtsa cells. Published by Elsevier Ireland Ltd.