Our current studies suggest mitochondrial dysfunction causes oxygen-associated genomic DNA damage. Because oxygen serves as an essential factor for oxidative stress, a cause of genomic instability, we have been examining the effect of modulating ambient oxygen on de novo tumorigenesis. We have found that decreasing the ambient oxygen exposure of p53 null mice causes a striking delay in tumorigenesis. We are now investigating this phenomenon in further detail. As hypoxia is known to affect the cardiovascular system, we are monitoring its effect on cardiovascular health for potential side-effects. These studies may provide insights into how modulation of ambient oxygen affects the course of tumorigenesis and have clinical implications.