adiation Biophysics

Our current radiation biophysics research mainly focuses on two areas, namely, (1) studying biological effects of alpha particles in vivo using zebrafish embryos, and (2) in vitro studies of radiation induced bystander effects.
Resources
Book chapter: Yu, K.N., Nikezic, D., "Alpha-Particle Radiobiological Experiments Involving Solid State Nuclear Track Detectors as Substrates", 2009, in Nuclear Track Detectors: Design, Methods and Applications, Eds. Maksim Sidorov and Oleg Ivanov, (Nova Science Publishers: New York) p. 133-154. (download pdf version) (purchase book)
Book chapter: Han, W., Yu, K.N., "Response of cells to ionizing radiation", 2009, in Advances in Biomedical Sciences and Engineering, Ed. S. C. Tjong, (Bentham Science Publishers: Illinois), Chapter 6, 204-262. (download pdf version) (purchase chapter/book)
Book chapter: Yu, K.N., Cheng, S.H., "In Vivo Studies of α-Particle Radiation Effects Using Zebrafish Embryos", 2009, in Advances in Biomedical Sciences and Engineering, Ed. S. C. Tjong, (Bentham Science Publishers: Illinois), Chapter 7, 263-283. (download pdf version) (purchase chapter/book)
Book chapter: Han, W., Yu, K.N., "Ionizing Radiation, DNA Double Strand Break and Mutation", 2010, in Advances in Genetics Research. Volume 4, Ed. Kevin V. Urbano, (Nova Science Publishers: New York), in press. (download pdf version) (purchase book)

 

Studying biological effects of alpha particles in vivo using zebrafish embryos

 

In vitro studies of radiation induced bystander effects (RIBE)

Generally, RIBE can be defined as the phenomenon that the irradiated cells (by α particles, X- or γ-ray, heavy ions etc.) can release some signaling molecule(s), which is transferred via the medium or gap-junctions, so that the same cytotoxicity or genotoxicity can be observed in the non-irradiated cells, which are either close to the irradiated cells or shared the conditioned medium harvested from the irradiated cells. RIBE has challenged the conventional dogma of radiation protection, the guidelines for which are based on prediction of biological effects of low doses of radiation by extrapolating from known epidemiological datasets.
 
Up-regulation of ROS by mitochondria-dependent bystander signaling
We used normal (ρ+) and mtDNA-depleted (ρ0) human-hamster hybrid cells to investigate mitochondrial effects on the genotoxicity in bystander effect through medium transfer experiments. Through the detection of DNA double-strand breaks with γ-H2AX, we found that the fraction of γ-H2AX positive cells changed with time when irradiation conditioned cell medium (ICCM) were harvested. We also treated cells with dimethylsuphoxide (DMSO), the scavenger of ROS, and quenched γ-H2AX induction by ρ+ ICCM. The work suggested that up-regulation of the mitochondria-dependent ROS might be very important in mediating genotoxicity of bystander effects.

The irradiated cells initiated intercellular bystander signaling with a mitochondrial-dependent pathway in the early phase, which would stimulate the up-regulation of ROS level in bystander cells. Up-regulated ROS would be responsible for increasing bystander DSBs, and misrepaired and unrepaired multiple DSBs might be relevant with chromosome aberration by deletion and involved in delayed genomic instability in bystander cells.
 
Exogenous carbon monoxide protects bystander cells
The inhibitory effect of carbon monoxide (CO), generated by Ticarbonyldichlororuthenium (II) dimer (CORM-2), on the toxicity of radiation induced bystander effect (RIBE) after α-particle irradiation was studied in a mixed co-culture system. CO (CORM-2) treatment showed a significant inhibitory effect to the formation of p53 binding protein 1 (BP1) and micronuclei (MN) induced by RIBE in a concentration dependent manner, but in the directly irradiated cell population no distinct decreases of BP1 and MN formation were observed. In this mixed co-culture system, nitric oxide (NO) or superoxide anion (O2-) was also proved to mediate the transduction of RIBE by using a NO synthase inhibitor or NAD(P)H-oxidase specific inhibitor treatment. The elevated O2- was attenuated by CO (CORM-2) treatment in the bystander cells as measured by hydroethidine staining and fluorescence assessment. The exogenous NO (sper) or O2- (H2O2) were used to mimic NO/O2-mediated RIBE, and CO (CORM-2) treatment also showed a protective effect to cells against the toxicity of these exogenous factors. Considering the inhibitory effect of CO on RIBE and the wide use of CO in therapy of diseases, it is hoped that a low concentration of CO can protect normal tissues against RIBE during radiotherapy.
 
Influence of natural antioxidants on bystander effect

We studied alpha-particle induced and medium-mediated bystander effects in Chinese hamster ovary (CHO) cells through cytokinesis-block micronucleus (CBMN) assay and terminal dUTP transferase-mediated nick end-labeling (TUNEL) assay. We studied the effects of natural antioxidants, which could scavenge reactive oxygen species (ROS), on the bystander effect. The studied natural antioxidants included catechins and Magnolol.

Catechins, a polyphenolic compound of green tea, are well-known as scavengers of ROS in human or mammalian cells. (–)-epigallocatechin gallate (EGCG), which is a major constituent of green tea catechins, is the most active antioxidant component with its effects seen at micromolar concentrations. The biological benefits of EGCG are generally attributed to their antioxidant activity to scavenge free-radical oxygen.

Magnolol is a natural active component with strong antioxidant properties extracted from the bark of Magnolia officinalis, and the bark of Magnolia officinalis is commonly used in traditional Chinese medicine and Japanese remedies. Apart from its antioxidant properties, it has lots of pharmacological effects including an anti-tumor capacity, anti-platelet aggregation, anti-fungal, anti-bacterial and anti-inflammatory effects.

With the presence of catechins or Magnolol, the percentage of bystander cells with MN formation and DNA strand breaks was decreased. The protection effect of these natural antioxidants on bystander cells from radiation has thus been demonstrated.

Leaves, bark and flower of Magnolia officinalis.

(from www.itmonline.org/ image/mag1.jpg)

 

Chemical structure of Magnolol.
  Publications
  • Chan, K.F., Yum, E.H.W., Wan, C.K., Fong, W.F., Yu, K.N., "Feasibility study on the use of polyallyldiglycol-carbonate cell dishes in TUNEL assay for alpha-particle radiobiological experiments", 2007, Nuclear Instruments and Methods in Physics Research B, 262, 128–134.
  • Chan, K.F., Yum, E.H.W., Wan, C.K., Fong, W.F., Yu, K.N., "Study of DNA integrity in alpha-particle radiobiological experiments using thin CR-39 detectors", 2008, Radiation Measurements, 43 (Suppl. 1), S541-S545.
  • Chen,S., Zhao, Y., Zhao, G., Han, W., Bao, L., Yu, K.N., Wu, L., 2009. Up-regulation of ROS by mitochondria-dependent bystander signaling contributes to genotoxicity of bystander effects, Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis, 666, 68-73.
  • Law, Y.L., Yu, K.N., 2009. Study of influence of catechins on bystander responses in alpha-particle radiobiological experiments using thin PADC films. Radiation Measurements, 44, 1069-1072.
  • Wong, T.P.W., Tse, A.K.W., Fong, W.F., Yu, K.N., 2009. Studying effects of Magnolol on alpha-particle induced bystander effects using PADC-film based dishes. Radiation Measurements, 44, 1081–1084.
  • Han, W., Chen,S., Yu, K.N., Wu, L., 2010. Nitric Oxide Mediated DNA Double Strand Breaks Induced in Proliferating Bystander Cells after Alpha-Particle Irradiation. Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis, 684, 81-89.
  • Han, W., Wu, L., Chen,S., Yu, K.N., 2010. Exogenous Carbon Monoxide Protects the Bystander Chinese Hamster Ovary Cells in Mixed Co-Culture System after Alpha-Particle Irradiation. Carcinogenesis, 31, 275-280.
  • Wong, T.P.W., Law, Y.L., Tse, A.K.W., Fong, W.F., Yu, K.N., 2010. Influence of Magnolol on the bystander effect induced by alpha-particle irradiation. Applied Radiation and Isotopes, 68, 718-721.
  • Law, Y.L., Wong, T.P.W., Yu, K.N., 2010. Influence of catechins on bystander responses in CHO cells induced by alpha-particle irradiation. Applied Radiation and Isotopes, 68, 726-729.
  • Chen, S., Zhao, Y., Han, W., Chiu, S.K., Zhu, L., Wu, L., Yu, K.N., 2010. Rescue effects in radiobiology: unirradiated bystander cells assist irradiated cells through intercellular signal feedback. Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis, 706, 59-64. 
  • Han, W., Yu, K.N., Wu, L.J., Wu, Y.C., Wang, H.Z., 2011. Mechanism of Protection of Bystander Cells by Exogenous Carbon Monoxide: Impaired Response to Damage Signal of Radiation-Induced Bystander Effect. Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis, 709-710, 1-6.

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Nuclear Radiation Unit
Department of Physics and Materials Science
City University of Hong Kong
Tat Chee Ave, Kowloon Tong, Hong Kong
Email: apnru@cityu.edu.hk

 

Page last modified on 17-Jan-2012

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