The overall goal of these studies is to understand how hypoxia and thiol depletion can modulate the responses of cells to cytotoxic therapy, the repair of misonidazole induced DNA damage under thiol depletion and supplementation will be correlated with cytotoxicity. Additional studies with model alkylating agents, EMS and L-PAM, will be done to compare the responses of normally aerated cells with hypoxic and reoxygenated cells. Experiments will also be performed to extend assessment of the relative resistance of hypoxic cells and reoxygenated cells to teniposide To assess cytotoxicity, colony formation assays will be used. DNA repair in EMT 6 mouse mammary tumor cells will be determined using alkaline elution techniques.
