The project investigates mechanisms by which human airway epithelial cells respond to ionizing radiation, especially a-particles like those implicated in the development of lung cancer in individuals exposed to radon and radon daughter products. The research considers how responses to a-emitters may be modified by reactive oxygen species (ROS) and other conditions that likely occur in vivo along with radon and radon daughter exposure. Mechanisms that cause postexposure delays in G1 phase will be investigated because: 1) such delays may provide cells with additional time to repair damaged DNA before DNA replication, and 2) escape from the G1 checkpoint or limitation of the otherwise normal duration of the G1 checkpoint in response to a given level of DNA damage may limit the repair efficiency of damaged DNA before initiation of replication. Results from this project expectedly will provide an explanation about how genomic alterations caused by ionizing radiations may go unrepaired and become heritable. Moreover, our results concerning ROS will expand our understanding of the roles ROS may play in the development of lung cancer following exposure to particles. Because the project relies heavily on flow cytometric approaches for cell-cycle analyses concurrently with analyses of immunofluorescence-labeled proteins, we are further developing our multiparameter flow cytometer and associated approaches for these measurements. We are also exploring the use of phase-sensitive-detection flow cytometry for such measurements.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR001315-14
Application #
5223169
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
14
Fiscal Year
1996
Total Cost
Indirect Cost
Frumkin, Jesse P; Patra, Biranchi N; Sevold, Anthony et al. (2016) The interplay between chromosome stability and cell cycle control explored through gene-gene interaction and computational simulation. Nucleic Acids Res 44:8073-85
Johnson, Leah M; Gao, Lu; Shields IV, C Wyatt et al. (2013) Elastomeric microparticles for acoustic mediated bioseparations. J Nanobiotechnology 11:22
Micheva-Viteva, Sofiya N; Shou, Yulin; Nowak-Lovato, Kristy L et al. (2013) c-KIT signaling is targeted by pathogenic Yersinia to suppress the host immune response. BMC Microbiol 13:249
Ai, Ye; Sanders, Claire K; Marrone, Babetta L (2013) Separation of Escherichia coli bacteria from peripheral blood mononuclear cells using standing surface acoustic waves. Anal Chem 85:9126-34
Sanders, Claire K; Mourant, Judith R (2013) Advantages of full spectrum flow cytometry. J Biomed Opt 18:037004
Cushing, Kevin W; Piyasena, Menake E; Carroll, Nick J et al. (2013) Elastomeric negative acoustic contrast particles for affinity capture assays. Anal Chem 85:2208-15
Chaudhary, Anu; Ganguly, Kumkum; Cabantous, Stephanie et al. (2012) The Brucella TIR-like protein TcpB interacts with the death domain of MyD88. Biochem Biophys Res Commun 417:299-304
Marina, Oana C; Sanders, Claire K; Mourant, Judith R (2012) Correlating light scattering with internal cellular structures. Biomed Opt Express 3:296-312
Houston, Jessica P; Naivar, Mark A; Jenkins, Patrick et al. (2012) Capture of Fluorescence Decay Times by Flow Cytometry. Curr Protoc Cytom 59:1.25.1-1.25.21
Marina, Oana C; Sanders, Claire K; Mourant, Judith R (2012) Effects of acetic acid on light scattering from cells. J Biomed Opt 17:085002-1

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