An In Vitro Versus In Vivo Toxicogenomic Investigation of Prenatal Exposures to Tobacco Smoke

Iain A. Perry, 1 Keith J. Sexton, 1 Zoe¨ C. Prytherch, 1 Jason L. Blum, 2 Judith T. Zelikoff, 2 and Kelly A. Be´ruBe ´1 1School of Biosciences, Cardiff University, Museum Avenue, Cardiff, United Kingdom. 2Department of Environmental Medicine, NYU School of Medicine, NYU Langone Medical Centre, Tuxedo, New York.

Approximately 1 million women smoke during pregnancy despite evidence demonstrating serious juvenile and/ or adult diseases being linked to early-life exposure to cigarette smoke. Susceptibility could be determined by factors in previous generations, that is, prenatal or ‘‘maternal’’ exposures to toxins. Prenatal exposure to airborne pollutants such as mainstream cigarette smoke has been shown to induce early-life insults (i.e., gene changes) in Offspring that serve as biomarkers for disease later in life. In this investigation, we have evaluated genome-wide changes in the lungs of mouse Dams and their juvenile Offspring exposed prenatally to mainstream cigarette smoke. An additional lung model was tested alongside the murine model, as a means to find an alternative in vitro, a human tissue-based replacement for the use of animals in medical research. Our toxicogenomic and bioinformatic results indicated that in utero exposure altered the genetic patterns of the fetus, which could put them at greater risk for developing a range of chronic illnesses in later life. The genes altered in the in vitro, cell culture model were reflected in the murine model of prenatal exposure to mainstream cigarette smoke. The use of alternative in vitro models derived from human medical waste tissues could be viable options to achieve human endpoint data and conduct research that meets the remits for scientists to undertake the 3Rs practices.


EpiAirway (AIR-100-PC12), cigarette smoke, toxicogenomics, RM20s smoke engine, Database for Annotation, Visualization and Integrated Discovery (DAVID ), gene expression, microarray analysis, cell cycle, cell adhesion, calcium homeostasis

Materials Tested

3R4F reference filtered cigarettes

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