Journal
MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS
Volume 656, Issue 1-2, Pages 14-18Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.mrgentox.2008.06.013
Keywords
IL1B; SNP; Polymorphism; Lung; B[a]P; CSC
Funding
- Norwegian Research Council
- Norwegian Cancer Society and Margareth Solberg Legacy
Ask authors/readers for more resources
Environmental and occupational toxicants may induce pulmonary inflammation. Chronic inflammation has been linked to several human diseases and also to initiation and promotion of cancer. Generation of reactive oxygen/nitrogen species (ROS/RNS), secretion of cytokines, chemokines and pro-angiogenic factors are believed to play a role. Interleukin IL-1 beta, encoded by the IL1B gene, is a key cytokine produced and secreted by many cell types after activation by biological or chemical agents. Several polymorphisms in the IL1B gene have been identified, and some are associated with increased risk for lung cancer. Especially. the IL1B -31 T/C polymorphism has received attention. We have investigated the effect of the lung carcinogens cigarette-smoke condensate (CSC) and benzo[a]pyrene (B[a]P) on the promoters of the IL1B gene varying only at the site of the -31 TIC polymorphism. The promoter fragments containing either C or T were cloned in luciferase reporter vectors and transfected into human lung epithelial NCI-H2009 cells. The results show that treatment of the transfected cells with CSC or B[a]P induced the promoter significantly above the control level. Interestingly, the promoter with the wild-type allele T in position -31 showed the stronger induction when compared with the promoter with variant allele C in this position. Bioinformatics and DNA-protein analysis indicated the presence of a novel transcription-factor binding site and the formation of protein complexes at the C promoter. (C) 2008 Elsevier B.V. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available