Advanced in vitro exposure systems.

Application of a direct aerosol exposure system for the assessment of biological effects of cigarette smoke and novel tobacco product vapor on human bronchial epithelial cultures

3. May. 2018

https://doi.org/10.1016/j.yrtph.2018.05.004

Shinkichi Ishikawa∗, Kazushi Matsumura, Nobumasa Kitamura, Kanae Ishimori, Yuichiro Takanami, Shigeaki Ito

Scientific Product Assessment Center, R&D Group, Japan Tobacco Inc., 6-2 Umegaoka, Aoba-ku, Yokohama, Kanagawa 227-8512, Japan

The experimental setup for the aerosol exposure consisted of a VC 10 smoking robot, a dilution system, and a Vitrocell 12/3 glass module the exposure of nicotine and TPM in the mainstream aerosols from 3R4F and novel tobacco vapor on MucilAir™ cells. The results are shown in cytotoxicity, IL-8, IL-1ß and gene expression.


ABSTRACT
Recent advancements in in vitro exposure systems and cell culture technology enable direct exposure to cigarette smoke (CS) of human organotypic bronchial epithelial cultures. MucilAir organotypic bronchial epithelial cultures were exposed, using a Vitrocell exposure system, to mainstream aerosols from the 3R4F cigarette or from a recently developed novel tobacco vapor product (NTV). The exposure aerosol dose was controlled by dilution flow and the number of products smoked; there were five exposure conditions for 3R4F smoke and three for NTV vapor. The amount of nicotine delivered to the tissues under each condition was analyzed and that of the total particulate matter (TPM) was estimated using nicotine data. The nicotine dose was similar for the two products at the highest dose, but the estimated TPM levels from the NTV were 3.7 times the levels from the 3R4F. Following 3R4F smoke exposure, a dose dependent increase was observed in cytotoxicity, cytokine secretion, and differential gene expression. However, no changes were detected in these endpoints following NTV vapor exposure, suggesting the biological effects of NTV vapor are lower than those of conventional combustible CS. Our study design, which includes collection of biological data and dosimetry data, is applicable to assessing novel tobacco products.

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