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Using Nuclear Receptor Activity to Stratify Hepatocarcinogens
Citation:
SHAH, I. A., K. A. HOUCK, R. JUDSON, R. J. KAVLOCK, M. T. MARTIN, D. REIF, J. F. WAMBAUGH, AND D. J. DIX. Using Nuclear Receptor Activity to Stratify Hepatocarcinogens. Stefan Wolfl (ed.), PLOS ONE . Public Library of Science, San Francisco, CA, 6(2; (e14584)):1-11, (2011).
Impact/Purpose:
The rodent carcinogens had higher in vitro potency for human NR relative to non-carcinogens. Structurally diverse chemicals with similar NR promiscuity patterns weakly associated with the severity of rodent liver cancer progression. While these results do not prove the role of NR activation in human liver cancer, they do have implications for nuclear receptor chemical biology and provide insights into putative toxicity pathways. More importantly, these findings suggest the utility of in vitro assays for stratifying environmental contaminants based on a combination of human bioactivity and rodent toxicity.
Description:
Nuclear receptors (NR) are a superfamily of ligand-activated transcription factors that control a range of cellular processes. Persistent stimulation of some NR is a non-genotoxic mechanism of rodent liver cancer with unclear relevance to humans. Here we report on a systematic analysis of new in vitro human NR activity data on 309 environmental chemicals in relationship to their liver cancer-related chronic outcomes in rodents.
