BioProject

As part of the civil aviation safety program to define the adverse effects of ethanol on flying performance, we present results of our DNA microarray analysis of samples from a timecourse study of individuals given ethanol orally, and then evaluated by breathalyzer to monitor blood alcohol content (BAC). More...

As part of the civil aviation safety program to define the adverse effects of ethanol on flying performance, we present results of our DNA microarray analysis of samples from a timecourse study of individuals given ethanol orally, and then evaluated by breathalyzer to monitor blood alcohol content (BAC). At five blood alcohol levels, T1-T5, blood was drawn such that the samples represented 0%, 0.04%, 0.08% BAC, and return to 0.04%, and 0.02% BAC. Microarray analysis showed that changes in gene expression could be detected across the time-course. We verified these expression changes by quantitative polymerase chain reaction (qPCR). Candidate target genes identified from the microarray analysis were clustered by expression change pattern, examined for shared functions and functional network membership. Five coordinately expressed groups were revealed and functional analysis showed shared transcription factor binding sites and functions for members of the clusters. These functions include protein synthesis and modification, expected for changes in gene expression, hematological and immune functions, expected for a blood sample, and pancreatic and hepatic function, expected as response to ethanol. The results provide a first look at changing gene expression patterns in blood during acute increase of ethanol concentration and its depletion due to metabolism or excretion and demonstrate that it is possible to detect significant changes in gene expression using total RNA isolated from whole blood. The analysis approach for this study can be utilized as part of a workflow to identify target genes by timecourse changes in gene expression that may affect pilot performance. Overall design: Blood samples were collected from six male subjects given a mixture of orange and vodka such that their BAC would reach a maximum level of 0.08%. Five blood samples, T1-5, were taken from each subject, 0% prior to drinking alcohol, 0.04% and 0.08% as their BAC increased and 0.04% and 0.02% BAC as the alcohol concentration declined. Blood samples were taken from a control set of five male subjects drinking only orange juice. Five sample collections at times averaged from the ethanol blood draws were performed. Total RNA was isolated from all samples. All samples were hybridized to microarrays to examine gene expression changes over the timed exposure to ethanol. One experimental sample failed. The remaining samples for Subject 18, T1-3, T5 were included in the study. There are 29 arrays for the experimental samples and 25 arrays for the control set of samples. There are separate RMA files for the experimental series and for the control series. Less...