Genomic biomarkers of pulmonary exposure to tobacco smoke components.
BACKGROUND
Associations between smoking and the development of tobacco-related diseases in humans have historically been assessed by epidemiological studies. These studies are further complicated by the number of chemicals used in tobacco and individual smoking habits. An alternative approach is required to assess the biological responses.


OBJECTIVE
Toxicogenomics was carried out to identify early molecular markers for events in pulmonary injury resulting from tobacco smoke components (TSC) exposure.


METHODS
EpiAirway-100 cells were exposed at the air/liquid interface to representative particle (nicotine; cadmium) and vapour phase [formaldehyde (FA) and ethyl carbamate] components of cigarette smoke. Microarray technology was used to compare expression profiles of human genes associated with toxicity and drug resistance, from control and TSC-treated respiratory epithelium (n=5/dose).


RESULTS
Using the GEArray 'toxicology and drug resistance' microarray followed by significance analysis of microarray analysis, 42 mRNA transcripts were found to be significantly altered by the TSC exposure. The vapour [ethyl carbamate, FA and particle (nicotine, cadmium)] phase TSC exhibited differential transcriptional responses that could not be attributed to their chemical phase. The transcriptional changes could be classified according to a functional family, where ethyl carbamate, FA and cadmium classified as carcinogens, demonstrated the highest gene homology when compared with the noncarcinogen, nicotine.


CONCLUSIONS
Analysis of the microarray data and further confirmation (reverse transcriptase-PCR) identified three potential biomarkers for TSC-induced injury. These three genes (CYP7A1, HMOX1 and PTGS1) are highly upregulated and have been linked with mechanistic pathways of disease.
Sexton
Keith
K
Cardiff School of Biosciences, Cardiff University, Museum Avenue, Cardiff, Wales, UK. Sextonk@cardiff.ac.uk
Balharry
Dominique
D
BéruBé
Kelly A
KA
D015415:Biomarkers / Q000378:metabolism*; D002104:Cadmium / Q000032:analysis / Q000378:metabolism; D002790:Cholesterol 7-alpha-Hydroxylase / Q000235:genetics; D051545:Cyclooxygenase 1 / Q000235:genetics; D005786:Gene Expression Regulation; D051547:Heme Oxygenase-1 / Q000235:genetics; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D009538:Nicotine / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012906:Smoke; D012907:Smoking / Q000009:adverse effects; D014158:Transcription, Genetic; D015854:Up-Regulation; D014026:Nicotiana
D015415:Biomarkers; D012906:Smoke; D002104:Cadmium; D009538:Nicotine; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1; D002790:Cholesterol 7-alpha-Hydroxylase; D051545:Cyclooxygenase 1; C496511:PTGS1 protein, human