Systems approaches evaluating the perturbation of xenobiotic metabolism in response to cigarette smoke exposure in nasal and bronchial tissues.
Capturing the effects of exposure in a specific target organ is a major challenge in risk assessment. Exposure to cigarette smoke (CS) implicates the field of tissue injury in the lung as well as nasal and airway epithelia. Xenobiotic metabolism in particular becomes an attractive tool for chemical risk assessment because of its responsiveness against toxic compounds, including those present in CS. This study describes an efficient integration from transcriptomic data to quantitative measures, which reflect the responses against xenobiotics that are captured in a biological network model. We show here that our novel systems approach can quantify the perturbation in the network model of xenobiotic metabolism. We further show that this approach efficiently compares the perturbation upon CS exposure in bronchial and nasal epithelial cells in vivo samples obtained from smokers. Our observation suggests the xenobiotic responses in the bronchial and nasal epithelial cells of smokers were similar to those observed in their respective organotypic models exposed to CS. Furthermore, the results suggest that nasal tissue is a reliable surrogate to measure xenobiotic responses in bronchial tissue.
Philip Morris International R&D, Philip Morris Products SA, Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland.
Anita R
AR
Iskandar
Florian
F
Martin
Marja
M
Talikka
Walter K
WK
Schlage
Radina
R
Kostadinova
Carole
C
Mathis
Julia
J
Hoeng
Manuel C
MC
Peitsch
D002478:Cells, Cultured; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008954:Models, Biological; D009297:Nasal Mucosa / Q000378:metabolism; D009666:Nose / Q000187:drug effects* / Q000473:pathology; D018570:Risk Assessment; D012906:Smoke / Q000009:adverse effects*; D012907:Smoking / Q000009:adverse effects* / Q000378:metabolism / Q000473:pathology; D015262:Xenobiotics / Q000378:metabolism
D012906:Smoke; D015262:Xenobiotics