Abstract

Cellular progression towards the cancerous state frequently is associated with the loss of genomic integrity, expressing as variable genomic changes i.e. instability. The purpose of this study is to provide insights into the molecular, genetic, cytogenetic and cellular processes that maintain genomic integrity or promote genomic instability in cells surviving exposure to ionizing radiation. Specifically this study investigates directly whether the originating event is located intra-or extranuclearly. Chromosomal instability is studied in hamster-human hybrid cells containing human chromosome 4 using fluorescence in situ hybridisation. The unique capabilities of the microbeam allow for the irradiation of cells with alpha-particles through subcellular compartments. Individual cells were imaged and irradiated with 1, 4, 8 , or 16 alpha particles through the nuclear centroid or through the cytoplasm .Cells were maintained in culture for 20-30 cellular divisions as individual clones. Chromosomally aberrant sub-clones were found for nuclear and cytoplasmic irradiations.It is highly probable that a DNA double strand break is not the most efficient initiator of genomic instability.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR011623-03
Application #
6123412
Study Section
Project Start
1998-09-01
Project End
1999-08-31
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
3
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
Columbia University (N.Y.)
Department
Type
DUNS #
167204994
City
New York
State
NY
Country
United States
Zip Code
10032

  Publications

Chai, Y; Calaf, G M; Zhou, H et al. (2013) Radiation induced COX-2 expression and mutagenesis at non-targeted lung tissues of gpt delta transgenic mice. Br J Cancer 108:91-8
Chai, Y; Lam, R K K; Calaf, G M et al. (2013) Radiation-induced non-targeted response in vivo: role of the TGFýý-TGFBR1-COX-2 signalling pathway. Br J Cancer 108:1106-12
Hu, Burong; Grabham, Peter; Nie, Jing et al. (2012) Intrachromosomal changes and genomic instability in site-specific microbeam-irradiated and bystander human-hamster hybrid cells. Radiat Res 177:25-34
Hei, Tom K; Zhao, Yongliang; Zhou, Hongning et al. (2011) Mechanism of radiation carcinogenesis: role of the TGFBI gene and the inflammatory signaling cascade. Adv Exp Med Biol 720:163-70
Hei, Tom K; Ballas, Leslie K; Brenner, David J et al. (2009) Advances in radiobiological studies using a microbeam. J Radiat Res 50 Suppl A:A7-A12
Brenner, David J (2008) The linear-quadratic model is an appropriate methodology for determining isoeffective doses at large doses per fraction. Semin Radiat Oncol 18:234-9
Hei, Tom K; Zhou, Hongning; Ivanov, Vladimir N et al. (2008) Mechanism of radiation-induced bystander effects: a unifying model. J Pharm Pharmacol 60:943-50
Chai, Yunfei; Hei, Tom K (2008) Radiation Induced Bystander Effect in vivo. Acta Med Nagasaki 53:S65-S69
Ponnaiya, Brian; Jenkins-Baker, Gloria; Randers-Pherson, Gerhard et al. (2007) Quantifying a bystander response following microbeam irradiation using single-cell RT-PCR analyses. Exp Hematol 35:64-8
Hei, Tom K (2006) Cyclooxygenase-2 as a signaling molecule in radiation-induced bystander effect. Mol Carcinog 45:455-60

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