|Topic:||18. Lung Cancer, Thoracic Oncology / Adult / Cellular/Molecular Investigation / Respiratory Cell and Molecular Biology (RCMB)|
|Authors:||J.C. Greenwell, J.D. Ritzenthaler, E. Torres-Gonzalez, W.H. Watson, J. Roman; Louisville, KY/US|
Introduction: Lung cancer is the leading cause of cancer death in both men and women worldwide. Epidemiological studies consistently reveal that lung cancer occurs primarily in the elderly. Interestingly, in never-smokers, it occurs more frequently in women. Unfortunately, studies investigating the role of aging and sex-dependent hormones have failed to reveal a dominant factor that explains these phenomena. One abnormality associated with aging and human disease risk is oxidation of the plasma redox potential (Eh) of the extracellular cysteine/cystine (Cys/CySS) pool.
Hypothesis: We hypothesized that alterations in Eh Cys/CySS could explain the increased susceptibility of the elderly and of females to lung cancer.
Methods: In vivo studies were performed by injecting 1E6 Lewis Lung Carcinoma (LLC) cells in PBS, subcutaneously into the hind flank of young and old C57BL/6 mice. Plasma was isolated retro-orbitally, from mice under anesthesia, using heparinized micro-hematocrit capillary tubes. Samples were analyzed by HPLC. Redox potentials were calculated from concentrations of Cys and CySS, using the Nernst equation. Mice were placed on a diet of differing sulfur amino acid content (Envigo; Indianapolis, IN) for 6 months.
Results: We observed a more oxidized plasma Eh Cys/CySS in female mice compared to males, but no change was observed with regard to age, up to 12 months. Interestingly, aged female mice were more susceptible to lung cancer metastasis in a xenograft model of lung cancer when compared to aged males. By altering the sulfur amino acid content of their diets, we were able to obtain a more reduced plasma Eh Cys/CySS. These changes, however, had no effect on lung cancer metastasis in our model.
Conclusions: Overall, these studies support the concept that aging and sex are important contributing factors in lung cancer progression. Although alterations in plasma Eh Cys/CySS were observed with regard to sex, this did not explain the increased susceptibility for lung cancer progression in females.