Ah receptor-independent induction of CYP1A2 gene expression in genetically inbred mice

Abstract

Acenaphthylene is a tricyclic aromatic hydrocarbon which induces hepatic methoxyresorufin O-demethylase (MROD) activity and CYP1A2 mRNA levels in 2 week-old male B6C3F1 mice. In the present study, this induction response was further investigated in genetically-inbred mice which differ in their aryl-hydrocarbon (Ah)-responsiveness. Acenapthylene (300 mg/kg) induced a 5- to 23-fold induction of MROD activity in Ah-nonresponsive (DBA and SJL) and responsive (C3H, C57/BL6, A/J, CBA and B6C3F1) mice. The highest induction response was observed in the DBA strain in which there was a 23- and 15-fold increase in activity in males and females, respectively. Acenaphthylene also caused a 2-fold increase in CYP1A2 mRNA and immunoreactive protein levels in 2 week-old DBA mice; however, this induction response was not observed in 6 week-old animals. For example, MROD activity in 6 week-old DBA mice was induced <2-fold by acenaphthylene, mainly as a consequence of increased basal CYP1A2 expression and MROD activity which, at the age of 6 weeks, approached levels induced by acenaphthylene in the 2 week-old mice. This was also observed by immunohistochemical staining with CYP1A2 antibodies of 2 and 6 week-old hepatic tissue from treated and control mice which also showed that CYP1A2 induction was dependent on the age of the animals.