Tel.: (206) 548-4091
Fax: (206) 548-4829

e-mail: jschwart@u.washington.edu
Jeffrey L. Schwartz

• Radiation Cytogenetics
• DNA Repair
• Radiotherapy

Interchromosomal Recombination

Detection of Early Apoptosis with FISH

The inherent sensitivity of cells within a tumor plays an important role in the response of the tumor to therapy. Our studies have focused on elucidating the molecular basis for differences in the inherent radiation sensitivity of human tumor cells. We have shown that inherent radiation sensitivity differences reflect primarily alterations in chromosome organization and these alterations influence the repair of chromosome breaks. Present studies focus on studying the role of cell cycle checkpoints in response. Understanding the basis for differences in tumor radiosensitivity should aid in the development of biomarkers of response and new approaches to cancer therapy.

Radiation-Induced Chromosome Aberrations in Human Tumor Cell

There is considerable interest in identifying biomarkers of radiation exposure that not only provide information on dose but also distinguish low LET from high LET exposure. Two potential biomarkers that we have been studying are chromosome aberrations and mutations at the hprt locus. Both endpoints can distinguish radiation-induced alterations from those that occur spontaneously or those induced by most chemical agents. There also appear to be LET-specific alterations in the types of induced chromosome aberrations. Present studies are focused on the influence of cell cycle stage and DNA repair on the frequency and types of mutations induced by radiation. These studies should aid in the development of better models of radiation action, and perhaps suggest approaches for chemoprevention.

DNA Sequence of Mutated HPRT Gene

Genomic instability is defined as the increased rate of acquisition of alterations in the mammalian genome. The induction of genome instability is considered an important prerequisite to cancer formation. Genome instability has also been suggested to contribute to the development of resistance to cancer therapy. Instability can develop spontaneously or it can also be induced by exposure to agents such as ionizing radiation. The goal of our studies is to identify markers of instability and use these markers to examine the hypothesis that instability is induced in tumors during a standard fractionated radiation treatment, and that this induced genome instability contributes to radiotherapy resistance.

Telomere Size in Stable and Unstable Clones of WTK1 Cells.