P53 is an important gene in the regulation of aerobic metabolism and may play a central role in energy production during exercise. In response to intracellular DNA damage, P53 can initiate a series of cell responses and may even fail to function properly. This preliminary investigation was designed to test the hypothesis that high intensity single leg exercise can cause extensive cell DNA damage, which subsequently may affect the expression of the P53 gene. Six (n=6) apparently healthy male participants (age 27 + 7years, stature 174 + 12cm, body mass 79 + 4kg and BMI 24 + 4kg/m2) completed 100 isolated and continuous maximal concentric contractions (minimum force = 200 N, speed of contraction = 60°/sec) of the rectus femoris muscle. Using a spring-loaded and reusable Magnum biopsy gun with a 16-gauge core disposable biopsy needle, human skeletal muscle micro biopsy tissue samples were extracted at rest and following exercise. mRNA gene expression was determined via two-step quantitative real-time PCR using GAPDH as a reference gene. The average muscle force production was 379 + 179 N. High intensity exercise increased mitochondrial 8-OHdG concentration (P < 0.05 vs. rest, n=6) with a concomitant decrease in total antioxidant capacity (P < 0.05 vs. rest, n=6). Exercise also increased protein oxidation as quantified by protein carbonyl concentration (P < 0.05 vs. rest, n=6). P53 expression increased following exercise, however, due to low subject numbers this change was not significant (P > 0.05, n=2) These preliminary findings tentatively suggest that maximal concentric muscle contractions can cause intracellular DNA damage with no apparent disruption to P53 gene expression. However, a large-scale study incorporating a greater subject number is warranted to fully elucidate this relationship.