Speaker
Mrs
Sara Skiöld
(Stockholm University)
Description
About 20% of patients receiving radiotherapy will develop adverse reactions to the therapy and 5% of these patients will develop severe reactions. Theoretically, all cancers could be controlled if a sufficiently high radiation dose could be delivered to the target. However, doses used in radiotherapy are adapted to the tolerance of the most sensitive patients. Thus, radiotherapy would greatly benefit from a diagnostic tool providing information on individual radiosensitivity.
The long term goal of this project is to provide diagnostic tools to help to individualize the therapy to improve tumor control, thus providing patients with better quality of life and reducing the health care costs.
Low linear energy transfer ionizing radiation produces a wide spectrum of DNA damages. The majority of the primary radiation effects are mediated by reactive oxygen species (ROS). The dominant forms of radiation-induced base modifications include 8-oxo-dG. If 8-oxo-dG is formed in DNA it can lead to GC→TA transversions. However, the nucleotide pool is also a target of ROS, where 8-oxo-dGTP can be formed. 8-Oxo-dGTP can be incorporated into DNA opposite an A, which can lead to AT→CG mutations1.
We have previously shown that urinary 8-oxo-dG could be used as a marker for individual radiosensitivity in breast cancer patients2. We think that the observed differences in urinary levels of 8-oxo-dG in breast cancer patients undergoing radiotherapy may reflect individual capacity to handle oxidative stress induced by radiation in the exposed healthy tissue. Based on our previously published data, we hypothesized that leucocytes in whole blood from sensitive patients can be used to monitor their repair capacity of 8-oxo-dGTP formed in response to radiation.
To test this hypothesis we have developed a highly sensitive ELISA assay for determination of serum level of 8-oxo-dG as a biomarker of oxidative stress. Whole blood were collected from radiosensitive and non-sensitive breast cancer patients and exposed to gamma radiation. The serum level of 8-oxo-dG was monitored for each individual in exposed and non-exposed samples. The result indicates that this assay may have the potential to be used to identify the most sensitive patients.
1) Evans M D, et al., Mutat Res 2004; 567, 1-61.
2) Haghdoost S, et al. Int J Radiat Oncol Biol Phys 2001; 50, 405-410.
Primary author
Mrs
Sara Skiöld
(Stockholm University)
Co-authors
Prof.
Ingemar Näslund
(Karolinska University Hospital)
Prof.
Mats Harms-Ringdahl
(Stockholm University)
Dr
Siamak Haghdoost
(Stockholm University)
