Non-invasive saliva human biomonitoring: development of an in vitro platform

• Published in: Journal of exposure science & environmental epidemiology Vol. 27; no. 1; pp. 72 - 77
• Main Authors: Weber, Thomas J, Smith, Jordan N, Carver, Zana A, Timchalk, Charles
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.01.2017; Nature Publishing Group
• Subjects: 692/698/3008/3014; 704/172/169/895; Acinar cells; Analysis of Variance; Animals; Biological Assay; Biological monitoring; Biomarkers - metabolism; Biomonitoring; Chemical transport; Chlorpyrifos; Chlorpyrifos - analysis; Chlorpyrifos - metabolism; Clearances; Drug dosages; Environmental Monitoring; Epidemiology; Epithelial cells; Epithelial Cells - metabolism; Epithelium; Exocrine glands; Health aspects; In Vitro Techniques; In vitro tests; Insecticides - analysis; Insecticides - metabolism; Kinases; Laboratories; Lipids; Male; Medicine; Medicine & Public Health; Metabolism; Metabolites; Methods; Models, Biological; Organic chemicals; original-article; Pesticides; Proteins; Rats; Rats, Sprague-Dawley; Saliva; Saliva - metabolism; Salivary diagnostics; Salivary gland; Salivary glands; Screening; Tight junctions; Toxicity tests; α-Amylase; United States; salivary gland; biomonitoring; pesticides; tight junction
• ISSN: 1559-0631; 1559-064X; 1559-064X
• DOI: 10.1038/jes.2015.74

Direct measurements of exposure represent the most accurate assessment of a subject’s true exposure. The clearance of many drugs and chemicals, including pesticides such as chlorpyrifos (CPF), can be detected non-invasively in saliva. Here we have developed a serous-acinar transwell model system as an in vitro screening platform to prioritize chemicals for non-invasive biomonitoring through salivary clearance mechanisms. Rat primary serous-acinar cells express both α -amylase and aquaporin-5 proteins and develop significant tight junctions at postconfluence — a feature necessary for chemical transport studies in vitro . CPF exhibited bidirectional passage across the serous-acinar barrier that was disproportional to the passage of a cell impermeable chemical (lucifer yellow), consistent with a hypothesized passive diffusion process. CPF was metabolized to trichlorpyridinol (TCPy) by serous-acinar cells, and TCPy also displayed bidirectional diffusion in the transwell assay. This model system should prove useful as an in vitro screening platform to support the non-invasive monitoring of toxicons and pharmacons in human saliva and provide guidance for development of advanced in vitro screening platforms utilizing primary human salivary gland epithelial cells.