title: The Bioavailability of Soluble Cigarette Smoke Extract Is Reduced through Interactions with Cells and Affects the Cellular Response to CSE Exposure.
abstract: Cellular exposure to cigarette smoke leads to an array of complex responses including apoptosis, cellular senescence, telomere dysfunction, cellular aging, and neoplastic transformation. To study the cellular response to cigarette smoke, a common in vitro model exposes cultured cells to a nominal concentration (i.e. initial concentration) of soluble cigarette smoke extract (CSE). However, we report that use of the nominal concentration of CSE as the only measure of cellular exposure is inadequate. Instead, we demonstrate that cellular response to CSE exposure is dependent not only on the nominal concentration of CSE, but also on specific experimental variables, including the total cell number, and the volume of CSE solution used. As found in other similar xenobiotic assays, our work suggests that the effective dose of CSE is more accurately related to the amount of bioavailable chemicals per cell. In particular, interactions of CSE components both with cells and other physical factors limit CSE bioavailability, as demonstrated by a quantifiably reduced cellular response to CSE that is first modified by such interactions. This has broad implications for the nature of cellular response to CSE exposure, and for the design of in vitro assays using CSE.
authors.affiliation: Department of Biology, College of the Holy Cross, Worcester, MA, 01610, United States of America.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Bourgeois
authors.affiliation: Department of Biology, College of the Holy Cross, Worcester, MA, 01610, United States of America.
authors.forename: Jeeva
authors.initials: J
authors.lastname: Jacob
authors.affiliation: Department of Biology, College of the Holy Cross, Worcester, MA, 01610, United States of America.
authors.forename: Aram
authors.initials: A
authors.lastname: Garewal
authors.affiliation: Department of Biology, College of the Holy Cross, Worcester, MA, 01610, United States of America.
authors.forename: Renata
authors.initials: R
authors.lastname: Ndahayo
authors.affiliation: Department of Biology, College of the Holy Cross, Worcester, MA, 01610, United States of America.
authors.forename: Julia
authors.initials: J
authors.lastname: Paxson
mesh_terms: D000818:Animals; D001682:Biological Availability; D016922:Cellular Senescence / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects*; D005347:Fibroblasts / Q000187:drug effects*; D051379:Mice; D041681:NIH 3T3 Cells; D015398:Signal Transduction / Q000187:drug effects; D012906:Smoke
chemical_list: D012906:Smoke