Aryl hydrocarbon receptor polymorphism modulates DMBA-induced inflammation and carcinogenesis in phenotypically selected mice

Vinicius R C De Souza, Wafa K. Cabrera, Antonella Galvan, Orlando G. Ribeiro, Marcelo De Franco, Francises Vorraro, Nancy Starobinas, Solange Massa, Tommaso A. Dragani, Olga M. Ibañez

Research output: Contribution to journalArticle

Abstract

We tested the role of aryl hydrocarbon receptor (Ahr) gene polymorphism in the inflammatory response and in skin and lung tumori genes is in 2 lines of mice phenotypically selected for maximum or minimum acute inflammatory reaction (AIRmax and AIRmin, respectively). Following 7,12-dimethylbenz[a]anthracene (DMBA) treatment, AIRmin but not AIRmax mice showed early skin reactions and eventually developed malignant skin tumors and lung adenocarcinomas. In skin tissue, transcript levels of ILlβ, Tnf, 06, Tgfβ 1 and Cyplbl genes were unregulated in AIRmin but not AIRmax mice, consistent with the inflammatory responses to the carcinogen. These findings appeared to be related to the homozygosity status of the Ahr functional A375V polymorphism, which influences the binding capability of the receptor for DMBA; the 375A allele, encoding the high-affinity ligand-binding receptor (Ahrb1), segregated in AIRmin mice, whereas AIRmax mice carried the 375V, corresponding to the low-affinity binding receptor (Ahrd), to DMBA. The differential segregation of Ahr functional Ahrd versus Ahrb1 alleles in AIRmax and AIRmin suggests a role for the Ahr gene in the control of inflammatory responsiveness and tumor development of these mouse lines,

Original languageEnglish
Pages (from-to)1478-1482
Number of pages5
JournalInternational Journal of Cancer
Volume124
Issue number6
DOIs
Publication statusPublished - Mar 15 2009

Keywords

  • Aryl hydrocarbon receptor
  • DMBA
  • Inflammation; carcinogenesis
  • Selected mice

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

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  • Cite this

    De Souza, V. R. C., Cabrera, W. K., Galvan, A., Ribeiro, O. G., Franco, M. D., Vorraro, F., Starobinas, N., Massa, S., Dragani, T. A., & Ibañez, O. M. (2009). Aryl hydrocarbon receptor polymorphism modulates DMBA-induced inflammation and carcinogenesis in phenotypically selected mice. International Journal of Cancer, 124(6), 1478-1482. https://doi.org/10.1002/ijc.24066