Project description:As part of the West Virginia Chemical Spill research program, NTP evaluated three chemicals that were spilled into the Elk Rever in West Virginia for their ability to cause toxicity or biological changes in a short-term toxicogenomic study
Project description:This study investigates the transcriptomic responses of Saccharomyces cerevisiae S96 normal and petite cells to 4-Methylcyclohexanemethanol (MCHM), a coal cleaning chemical spilled in the water supply of central West Virginia in 2014.
Project description:The large-scale chemical spill on January 9, 2014 from coal processing and cleaning storage tanks of Freedom Industries in Charleston affected the drinking water supply to 300,000 people in Charleston, West Virginia metropolitan, while the short-term and long-term health impacts remain largely unknown and need to be assessed and monitored. There is a lack of publically available toxicological information for the main contaminant 4-methyl-1-cyclohexanemethanol (4-MCHM). Particularly, little is known about 4-MCHM metabolites and their toxicity. This study reports timely and original results of the mechanistic toxicity assessment of 4-MCHM and its metabolites via a newly developed quantitative toxicogenomics approach, employing proteomics analysis in yeast cells and transcriptional analysis in human cells. These results suggested that, although 4-MCHM is considered only moderately toxic based on the previous limited acute toxicity evaluation, 4-MCHM metabolites were likely more toxic than 4-MCHM in both yeast and human cells, with different toxicity profiles and potential mechanisms. In the yeast library, 4-MCHM mainly induced chemical stress related to transmembrane transport and transporter activity, while 4-MCHM metabolites of S9 mainly induced oxidative stress related to antioxidant activity and oxidoreductase activity. With human A549 cells, 4-MCHM mainly induced DNA damage-related biomarkers, which indicates that 4-MCHM is related to genotoxicity due to its DNA damage effect on human cells and therefore warrants further chronic carcinogenesis evaluation.
Project description:We investigated the gene expression changes associated with skin pigmentation variation between Virginia opossum populations inhabiting tropical and temperate environments. We found that gene expression variation in genes with melanocytic and immune functions is associated with the degree of skin pigmentation variation. Further, we found evidence suggesting that the Wnt/ß-catenin signaling pathway might be regulating the depigmentation observed in temperate populations. We present several alternative hypotheses that may explain Gloger’s rule pattern of skin pigmentation variation in the Virginia opossum.
