title: 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.
authors.affiliation: Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX 77843-4466, USA.
authors.forename: M
authors.initials: M
authors.lastname: Gupta
authors.forename: J
authors.initials: J
authors.lastname: Miggens
authors.forename: A
authors.initials: A
authors.lastname: Parrish
authors.forename: J
authors.initials: J
authors.lastname: Womack
authors.forename: K S
authors.initials: KS
authors.lastname: Ramos
authors.forename: L V
authors.initials: LV
authors.lastname: Rodriguez
authors.forename: L S
authors.initials: LS
authors.lastname: Goldstein
authors.forename: C
authors.initials: C
authors.lastname: Holtzapple
authors.forename: L
authors.initials: L
authors.lastname: Stanker
authors.forename: S H
authors.initials: SH
authors.lastname: Safe