Acetaminophen-induced hepatotoxicity is associated with early changes in AP-1 DNA binding activity.
Blazka ME; Bruccoleri A; Simeonova PP; Germolec DR; Pennypacker KR; Luster MI
Res Commun Mol Pathol Pharmacol 1996 Jun; 92(3):259-273
A study examined changes associated with DNA AP-1 binding activities in the liver following administration of hepatotoxic doses of acetaminophen (103902) (APAP) to female B6C3F1-mice. Changes in the expression of early immediate genes and DNA binding activities of the AP-1 transcription factor were detected early in APAP hepatotoxicity and preceded conventional indicators of hepatotoxicity, such as liver associated serum enzymes. While serum enzyme levels returned to control values within 24 hours following APAP treatment, AP-1 DNA binding activity stayed at an elevated level for 24 additional hours. The authors conclude that this finding may reflect the role of AP-1 DNA binding activity in liver repair as AP-1 participates in cell proliferation and differentiation by positively and negatively regulating the transcription of genes containing AP-1 binding sites, in addition to being associated with cell injury. AP-1 was rapidly activated following partial hepatectomy. The authors note that even though all of the response elements activated by AL-1 binding have not been identified, and their exact role remains to be determined, these early molecular changes should prove to be useful molecular biomarkers.
NIOSH-Author; Liver-damage; Cytotoxic-effects; Laboratory-animals; Liver-enzymes; Protein-chemistry; Protein-synthesis; Genotoxic-effects
Research Communications in Molecular Pathology and Pharmacology