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Aryl hydrocarbon receptor polymorphism modulates DMBA‐induced inflammation and carcinogenesis in phenotypically selected mice
Author(s) -
De Souza Vinicius R.C.,
Cabrera Wafa K.,
Galvan Antonella,
Ribeiro Orlando G.,
De Franco Marcelo,
Vorraro Francisca,
Starobinas Nancy,
Massa Solange,
Dragani Tommaso A.,
Ibañez Olga M.
Publication year - 2008
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.24066
Subject(s) - aryl hydrocarbon receptor , dmba , carcinogenesis , biology , cyp1b1 , receptor , carcinogen , cancer research , microbiology and biotechnology , gene , immunology , endocrinology , cytochrome p450 , genetics , transcription factor , metabolism
We tested the role of aryl hydrocarbon receptor ( Ahr ) gene polymorphism in the inflammatory response and in skin and lung tumorigenesis 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 IL1β, Tnf, Il6, Tgfβ1 and Cyp1b1 genes were upregulated 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 ( Ahr b1 ), segregated in AIRmin mice, whereas AIRmax mice carried the 375V, corresponding to the low‐affinity binding receptor ( Ahr d ), to DMBA. The differential segregation of Ahr functional Ahr d versus Ahr b1 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. © 2008 Wiley‐Liss, Inc.