title: Blood gene expression profiling of an early acetaminophen response.
abstract: Acetaminophen can adversely affect the liver especially when overdosed. We used whole blood as a surrogate to identify genes as potential early indicators of an acetaminophen-induced response. In a clinical study, healthy human subjects were dosed daily with 4 g of either acetaminophen or placebo pills for 7 days and evaluated over the course of 14 days. Alanine aminotransferase (ALT) levels for responders to acetaminophen increased between days 4 and 9 after dosing, and 12 genes were detected with expression profiles significantly altered within 24 h. The early responsive genes separated the subjects by class and dose period. In addition, the genes clustered patients who overdosed on acetaminophen apart from controls and also predicted the exposure classifications with 100% accuracy. The responsive genes serve as early indicators of an acetaminophen exposure, and their gene expression profiles can potentially be evaluated as molecular indicators for further consideration.
authors.affiliation: Microarray and Genome Informatics Group, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA.|Biostatistics Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA.
authors.forename: P R
authors.initials: PR
authors.lastname: Bushel
authors.affiliation: Molecular Genomics Core, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA.|Laboratory of Toxicology and Pharmacology, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA.
authors.forename: R D
authors.initials: RD
authors.lastname: Fannin
authors.affiliation: Molecular Genomics Core, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA.|Laboratory of Toxicology and Pharmacology, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA.
authors.forename: K
authors.initials: K
authors.lastname: Gerrish
authors.affiliation: The Hamner Institute for Health Sciences, Research Triangle Park, NC, USA.|Department of Medicine, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: P B
authors.initials: PB
authors.lastname: Watkins
authors.affiliation: Molecular Genomics Core, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA.|Laboratory of Toxicology and Pharmacology, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA.
authors.forename: R S
authors.initials: RS
authors.lastname: Paules
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage / Q000009:adverse effects*; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage / Q000009:adverse effects*; D015415:Biomarkers / Q000097:blood; D004334:Drug Administration Schedule; D062787:Drug Overdose / Q000097:blood / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D053263:Gene Regulatory Networks; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D020411:Oligonucleotide Array Sequence Analysis; D010597:Pharmacogenetics; D000071185:Pharmacogenomic Testing / Q000379:methods*; D000071184:Pharmacogenomic Variants; D012313:RNA / Q000097:blood / Q000235:genetics*; D016037:Single-Blind Method; D013997:Time Factors; D059467:Transcriptome; D055815:Young Adult
chemical_list: D018712:Analgesics, Non-Narcotic; D015415:Biomarkers; D000082:Acetaminophen; D012313:RNA; D000410:Alanine Transaminase