Zosky, GR and Ramsey, KA and Carter, KW and Bosco, A and McKenna, KL and Sly, PD, In utero arsenic exposure via drinking water alters genes related to lung growth and mucociliary function, Respirology, 2-6 April 2011, Perth, Australia, pp. 29. ISSN 1323-7799 (2014) [Conference Extract]
Rationale: Exposure to arsenic via drinking water is a global health problem. Recent studies suggest that early life arsenic exposure via drinking water increases the risk of mortality due to bronchiectasis in later life. We have shown previously that mice exposed to arsenic via drinking water in utero develop strain dependent alterations in post-natal lung mechanics. We aimed to explain these differences by exploring genetic pathways in the lung that are altered by exposure to arsenic.
Methods: Pregnant BALB/c, C57BL/6 and C3H/HeARC mice were exposed to 0 (control) or 100 μg.L−1 arsenic via drinking water from day 8 gestation (prior to development of the lung buds) until birth of their pups. At 2 weeks post-natal age mice had somatic growth and lung function (lung volume and mechanics) measured. Lung tissue was collected for gene expression analysis by microarray. Subsets of biologically plausible genes that were identifi ed as being differentially expressed by microarray were confi rmed by real-time PCR.
Results: C57BL/6 and C3H/HeARC mice had defi cits in lung tissue and airway mechanics respectively whereas lung function in BALB/c mice was not altered. C57BL/6 mice exposed to arsenic had genes related to mucous production up-regulated (Clca3, Muc5b) whereas C3H/HeARC mice had altered expression of genes related to lung morphogenesis (Sox2) and ciliary function (Ttc21a).
Conclusions: In utero arsenic exposure via drinking water altered genes related to both lung branching morphogenesis and mucociliary function. These alterations in expression correlated with changes in lung mechanics. The established association between arsenic exposure and mortality due to bronchiectasis may be explained by altered lung growth and/or mucociliary clearance.
|Item Type:||Conference Extract|
|Research Division:||Biomedical and Clinical Sciences|
|Research Group:||Cardiovascular medicine and haematology|
|Research Field:||Respiratory diseases|
|Objective Group:||Clinical health|
|Objective Field:||Clinical health not elsewhere classified|
|UTAS Author:||Zosky, GR (Professor Graeme Zosky)|
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