You are here:
Characterization of the Androgen-sensitive MDA-kb2 Cell Line for Assessing Complex Environmental Mixtures
Citation:
BLAKE, L. S., J. E. CAVALLIN, D. MARTINOVIC, L. E. GRAY, JR, V. S. WILSON, R. R. REGAL, DAN VILLENEUVE, AND G. T. ANKLEY. Characterization of the Androgen-sensitive MDA-kb2 Cell Line for Assessing Complex Environmental Mixtures. ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY. Society of Environmental Toxicology and Chemistry, Pensacola, FL, 29(6):1367-1376, (2010).
Impact/Purpose:
The results of our studies confirm the utility of the MDA cell line for quantifying the activity of mixtures of androgens in complex wastes such as municipal effluents and feedlot discharges.
Description:
Complex mixtures of synthetic and natural androgens and estrogens, and many other non-steroidal components are commonly released to the aquatic environment from anthropogenic sources. It is important to understand the potential interactive (i.e., additive, synergistic, antagonistic) effects of these mixtures in order to properly assess their risk. In these studies we used a human breast cancer cell line with endogenous androgen receptors and a stably-transfected luciferase reporter gene construct (MDA-kb2) to quantify the androgenic activity of natural and synthetic androgens. The androgens tested included testosterone, 17 17 androstenedione, dihydrotestosterone, methyl-testosterone, and trendione. We tested combinations of these androgens and compared the expected versus observed androgenic activity based on a concentration addition model. Our analyses confirm the hypothesis that the androgen receptor agonists cause additive responses when assessed as a mixture. Binary mixtures of 17and 17as well as triclocarban (an anti-microbial found in the environment) and 17e were also tested. 17induced activity at concentrations greater than those found in the environment, and triclocarban enhanced the activity of 17 Additionally, three anti-androgens were each paired with three androgens of varying potencies. The relative potencies of the antagonists were constant no matter the androgen used: vinclozolin metabolite (M2) > procymidone > prochloraz. The results of our studies confirm the utility of the MDA cell line for quantifying the activity of mixtures of androgens in complex wastes such as municipal effluents and feedlot discharges.