DNA Microarray Data Analysis

National Institute Of Environmental Health Sciences

Investigators

Linked publications, trials & patents

Abstract

As part of NTPs efforts to characterize polybrominated diphenyl ether (PBDE) toxicity, I previously helped to evaluate the transcriptional response to a PBDE mixture (DE-71) in liver samples of male and female rat pups, and male rats, in a study that associated DE-71-induced liver gene-transcript changes with lipid and metabolic pathways. We later investigated the transcriptomic changes in response to DE-71 and its congener, 2,2,4,4-tetra-bromodiphenyl ether (BDE-47), on postnatal day 4 and postnatal day 22 after in utero exposure/postnatal day exposure. We also compared the effects of three legacy and six emerging brominated flame retardants in male Sprague-Dawley rats following five-day exposure. A separate publication describes the large toxicogenomics data set generated to statistically compare control responses to those from multiple dose groups across the nine flame retardant chemicals and perform genomic benchmark dose calculations for each chemical. Transcripts underlying the Nrf2 antioxidant pathway were upregulated to the greatest extent after exposure to PBDE-47, but this pathway was also upregulated after decaBDE, HBCD, TBB and HCBCO exposure. The data for this study has been deposited in a separate publication. I am collaborating to synthesize the information obtained from these publications to discover the pathways and genes that are consistently activated in response to PBDE exposure. This project is ongoing. In another project, we exposed B6C3F1/N mice to cobalt metal dust (CMD) by inhalation to investigate rodent alveolar/bronchiolar carcinomas (ABCs). At a false discovery rate threshold of 0.05, a total of 11,557 transcripts were changed in spontaneous ABCs compared to controls, and 12,420 transcripts were changed in CMD exposed ABCs compared to controls.8,520 transcript changes were shared between spontaneous and CMD exposed changes. Transcriptomic analysis of ABCs that formed spontaneously or due to CMD exposure contained changes related to MAPK signaling and oxidative stress. The genes encoding Nox4 and Ereg was upregulated in CMD-exposed mice. The data here suggest that oxidative stress plays a significant role in CMD-induced pulmonary carcinogenesis in rodents, which may also be relevant in humans.