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

Mona Gupta, John Miggens, Alan Parrish, James Womack, Kenneth S. Ramos, Louis V. Rodriguez, Lawrence S. Goldstein, Carol Holtzapple, Larry Stanker, Stephen H. Safe

Research output: Contribution to journalArticle

3 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)205-213
Number of pages9
JournalEnvironmental Toxicology and Pharmacology
Volume5
Issue number3
DOIs
StatePublished - May 1 1998
Externally publishedYes

Keywords

  • Acenaphthylene
  • Ah receptor-independent
  • CYP1A2 induction
  • Mice

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology
  • Health, Toxicology and Mutagenesis

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    Gupta, M., Miggens, J., Parrish, A., Womack, J., Ramos, K. S., Rodriguez, L. V., Goldstein, L. S., Holtzapple, C., Stanker, L., & Safe, S. H. (1998). Ah receptor-independent induction of CYP1A2 gene expression in genetically inbred mice. Environmental Toxicology and Pharmacology, 5(3), 205-213. https://doi.org/10.1016/S1382-6689(98)00004-0