Blood Gene Expression Profiling of an Early Acetaminophen Response (II)

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 4g 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 24hrs. 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. Overdosed patients admitted to the emergency room. Five male and female individuals from 19 - 59 years old were admitted to the emergency room following an overdose on acetaminophen. The patients presented 12hrs to 4 days after ingestion. ALT and AST elevated peaking beyond 400 U/I and 120 U/I. Blood was collected 2 or 5 days following ingestion.