Radiation-induced genomic instability

1. Research group name/project:
Radiation-induced genomic instability

2. Group leader and some key members (incl. from other depts./inst.):
Jostein Dahle, Egil Kvam, Trond Stokke.

3. Home address on the internet:
http://radium.no/stokke

4. Department/Institute:
Department of Biophysics

4b. Hospital (HF):
Det norske radiumhospital HF

5. Main aim of research group:
The principal objective of the project is to determine the molecular mechanisms of ultraviolet radiation induced genomic instability to enable identification of targets for sun cream and drug development and biomarkers for disease monitoring.

6. Some important recent results (with a few key references):
This small project group has pioneered studies of genomic instability induced by ultraviolet radiation. Ultraviolet radiation-induced mutations have been assumed to be the result of DNA damage inflicted directly by the radiation. This DNA damage is converted to a mutation either during DNA replication or as the result of errors during DNA repair, and mutations should therefore occur shortly after irradiation. However, recent evidence from our lab suggests that increased mutation frequencies can occur 23 cell generations after ultraviolet irradiation. By cloning cells immediately after irradiation and culturing them for 23 cell generations before measuring mutation frequency, UVA radiation was found to be as effective as UVB radiation in inducing delayed mutations. Around 10 % of these cell clones exhibited increased delayed mutation frequencies. Thus, both UVA- and UVB radiation is able to disrupt cellular homeostasis such that the memory of past insult is perpetuated over multiple cellular generations. This result is quite remarkable because UVB radiation is around ten times more

7. Methods in current use:
HPRT mutation and genomic instability assay, fluorescence based detection of oxidative stress, HPLC detection of 8-oxo-guanine, Multiplex polymerase chain reaction, Sequencing, DNA repair deficient cell lines, green fluorescing protein mutation assay.

8. Available equipment:
Flow cytometer, fluorescence microscopes, high pressure liquid chromatography.

9. Collaborators:
9.1. Among Helse Sør hospitals : Olav Kaalhus, Manish Kakar, Harald B. Steen, Even Angell-Petersen, Svein-Ole Mikalsen, Edgar Rivedal, Karen Marie Heinz.
9.2. Other Norwegian collaborators: Gunnar Brunborg and Ann Karin Olsen, Institute of Public Health, Rune Blomhoff, Institute of Nutrition.
9.3. Collaborators from other countries: Bernd Epe, University of Mainz, Germany, Hatsumi Nagasawa, Harvard School of Public Healty, USA. Klaus Erixon, Arrhenius Laboratories, Sweden. Margaret Z. Zdzienicka, Leiden University, The Netherland

10. Some key search words:
Genomic instability, ultraviolet radiation, ionizing radiation, mutation, HPRT