PARENT SESSION
Work-in-Progress

(WIP-377) Does tumor microenvironment impact mutagenesis?

LaRue, Susan^*,1, Trncic, Nadira¹, Hall, Emily¹, McNiel, Elizabeth¹, Tumolo, Gregory¹, Waldren, Charles², ¹ Department of Radiological Health Sciences, Colorado State University, Fort Collins, CO² Radiation Effects Research Foundation, Hiroshima City, Japan

ABSTRACT-
The impact of tumor hypoxia on local tumor control has long been a concern for solid tumors treated with radiation therapy. More recent work has implied that hypoxia of the primary tumor may also be associated with metastatic spread, perhaps by contributing to genetic instability. It has been proposed that tumor microenvironment, with fluctuating hypoxia, low pH and nutrient deprivation may be responsible for diminished DNA repair and increased mutagenesis. We hypothesized that hypoxia, alone or in combination with other conditions found in tumor microenvironment could lead to genomic alterations. To investigate our hypothesis we used the A_L mutation assay. A_L cells are human-hamster hybrid cells, containing standard set of CHO-K1 chromosomes and single copy of human chromosome 11. Genetic markers on chromosome 11 have been mapped, including the CD59 gene that codes for a cell surface antigen, CD59. Wild type CD59+ cells are killed when the culture is treated with monoclonal antibody to the CD59 antigen and rabbit complement. Mutant CD59- cells survive to form colonies. Since human chromosome 11 is not essential for the viability of the hybrid cell, except for a small segment on the tip of short arm, mutations ranging from point mutation to loss of almost whole chromosome 11 can be detected. We exposed A_L cells for different times to hypoxia and other conditions. Results will be presented. Supported in part by:CA42745 and CA0936.

KEYWORDS: tumor, hypoxia, A_L cells, mutagenesis