Abstract 5434: Oxidative stress analysis in peripheral blood mononuclear cells of pediatric leukemia undergoing chemotherapy: Correlations with dietary intake

Abstract

Abstract Clinical observations suggest that poor nutrition worsens outcomes for pediatric leukemia patients undergoing therapy. However, the molecular basis for this observation is not well understood. Ample data indicates that increased cellular oxidative stress is an important mechanism of action of chemotherapeutic regimens used for pediatric acute leukemias. Reports also suggest that diet may modulate the balance of cellular pro- and antioxidants. Here, we propose that age appropriate adequate nutrition promotes endogenous metabolic sources of oxidative stress, which when combined with chemotherapy induced oxidative stress, provide better outcomes for these patients. Assessments of nutrition and oxidative stress were completed for each patient at regularly scheduled intervals over a six month period. Changes in nutrition and oxidative stress were monitored. Nutrition was quantified by conducting 24 hour dietary recalls. Data was entered into the Minnesota Nutrition Data System for Research (NDSR) dietary analysis program. Cellular oxidative stress in mononuclear cells isolated from peripheral blood was also quantified. Specifically, intracellular superoxide and hydrogen peroxide were measured with dihydroethidium (HE) and 2′,7α-dichlorofluorescin diacetate (DCF-DA) staining by flow cytometry, respectively. Glutathione (GSH), an antioxidant, was also measured by monochlorobimane staining. To date, analyses have been completed for 12 patients. An increase in superoxides was detected in 72.7% of patients (8 of 11). An increase in hydrogen peroxide was detected in 50% of patients (6 of 12). An increase was defined as a two-fold or greater elevation in ROS at any subsequent visit compared to the baseline visit. A decrease in GSH was seen in 50% of patients (6 of 12) and 33% (4 of 12) demonstrated a decrease in GSH coincident with an increase in both superoxides and hydrogen peroxide. This increase in ROS and decrease in GSH suggests that the majority of our patients experience oxidative stress during therapy. To investigate the impact of diet on oxidant status, NDSR software was used to compare the consumption of dietary antioxidants, such as vitamins A, B3, C, and E, selenium, and glutamic acid, to the corresponding amounts of ROS from the same visit. The strongest correlation was between vitamin C consumption and hydrogen peroxide levels. An inverse relationship between vitamin C consumption and hydrogen peroxide levels was apparent in 58.3% of patients (7 of 12). These data provide insight into the relationship between diet and oxidative stress in pediatric leukemia patients. Future work will support the design of dietary interventions that will modulate oxidant status to favor improved survival of children with leukemia. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5434. doi:1538-7445.AM2012-5434