EXPRESSIONS PROFILING PROJECT OF HUMAN EMBRYONIC LUNG CELLSEXPOSED TO PYROLYZED CIGARETTE SMOKEAbstract
In contrast to the problematic health and economic effects of acute and chronic smoke exposure on lung function and airway inflammation, there are still few data dealing with the effects of smoking. Smoke exposurecan result in aberrant cell growth. In our experiments, pyrolyzed components of cigarettes have been shown to induce a strong stress response in cultured cells. We used human embryonic lung (HEL) cells, which respond with an altered expression of a broad spectrum of genes. Therefore we performed a systematic analysis of the genetic expression behaviour, using the established whole genome microarray-technology which should be able to reveal the cellular effects. With these data we aim to generate a qualitative spectrum of cellular stress response activity. It is noticeable that after cells’ exposure to pyrolyzed tobacco smoke components the products of the most affected genes, e.g. ID1, inhibitor of DNA binding, are up-regulated as a rapid response after 2 h with a factor 3.8 and RPS2, ribosomal protein S2, is down-regulated to nearly 50 % after 24 hours. In databases they are documented as still uncharacterized and hypothetical proteins. The DDIT4 gene, encoding the DNA-damage-inducible transcript 4, associated with regulation and development of DNA processes after damage by ionizing radiation and in p53 mediated apoptotic processes, is up-regulated. The exposure leads to a rapid cellular stress response of genes like induction of the ID1, ID2, and ID3 genes, located on different chromosomes, already after two hours. They interact normally with DNA binding proteins under heterodimer formation and are considered as negative regulators of transcription. After 24 hours, a return back to normal was not observed and the genes remained stably down-regulated. The suppression of the GADD45B gene which is involved in the cell cycle regulation and after DNA damage a cell cycle arrest is mediated by the gene product. The C14orf4 gene (IRF2BPL) suggests a bifunctional role in transcription control as a promotor’s activator as well as a repressor. Recent data indicate a prominent role of this gene transcript in the control of female reproductive function. On balance, the role of the predominant amount of affected genes is focused on cellular stress response and DNA metabolism.
Klaus Braun*, Gabriele Müller , Matthias Schick , Melanie Bewerunge-Hudler , Oliver Heil , Manfred Wiessler , Rüdiger Pipkorn , Wolfhard Semmler and Waldemar Waldeck
Medical Physics in Radiology, Deutsches Krebsforschungszentrum (DKFZ), Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany
27 June, 2013
28 July, 2013
27 October, 2013
01 November, 2013