Monday, February 09, 2009

Low Levels of Arsenic in Drinking Water Causes Irreversible Damage to Lungs to Newborns

Toxicology and Applied PharmacologyVolume 235, Issue 1, 15 February 2009, Pages 105-113

In utero and postnatal exposure to arsenic alters pulmonary structure and function

R. Clark Lantza, b, c, , , Binh Chaua, Priyanka Sarihana, Mark L. Wittenb, d, Vadim I. Pivniouka, e and Guan Jie Chena
aDepartment of Cell Biology and Anatomy, University of Arizona, Tucson, AZ 85724, USA
bSouthwest Environmental Health Science Center, University of Arizona, Tucson, AZ 85721, USA
cBIO5 Institute, University of Arizona, Tucson, AZ 85721, USA
dDepartment of Pediatrics, University of Arizona, Tucson, AZ 85724, USA
eArizona Respiratory Center, University of Arizona, Tucson, AZ 85724, USA

In addition to cancer endpoints, arsenic exposures can also lead to non-cancerous chronic lung disease. Exposures during sensitive developmental time points can contribute to the adult disease. Using a mouse model, in utero and early postnatal exposures to arsenic (100 ppb or less in drinking water) were found to alter airway reactivity to methacholine challenge in 28 day old pups. Removal of mice from arsenic exposure 28 days after birth did not reverse the alterations in sensitivity to methacholine. In addition, adult mice exposed to similar levels of arsenic in drinking water did not show alterations. Therefore, alterations in airway reactivity were irreversible and specific to exposures during lung development. These functional changes correlated with protein and gene expression changes as well as morphological structural changes around the airways. Arsenic increased the whole lung levels of smooth muscle actin in a dose dependent manner. The level of smooth muscle mass around airways was increased with arsenic exposure, especially around airways smaller than 100 μm in diameter. This increase in smooth muscle was associated with alterations in extracellular matrix (collagen, elastin) expression. This model system demonstrates that in utero and postnatal exposure to environmentally relevant levels of arsenic can irreversibly alter pulmonary structure and function in the adults.
BrooklynDodger(s) comments: Risk assessors debate whether cancer causing properties discovered by one route apply (are relevent) to another - inhalation v. ingestion usually. Houdinists default to no relevence. Arsenic became known to be a human carcinogen as a result of inhalation exposure in the workplace causing lung cancer. Then as a result of ingestion of water in the developing world. Now comes laboratory support for human epidemiology. Also, this study shows the potential importance of looking at all stages of life. The Dodger(s) need to search for drinking water bioassays of arsenic. And, it would be nice if the investigators repeated the study with in utero only and perinatal only exposure.

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