DIETARY FLAXSEED AMELIORATES RADIATION PNEUMONOPATHY

IN MICE

James Lee¹, Keith Cengel², Stathis Kanterakis¹, Ryan Krochak¹, Evguenia Arguiri¹, C.C. Solomides³, and M.Christofidou-Solomidou¹: ¹Depts. of Medicine, and ²Radiaiton Oncology, University of Pennsylvania and ³Dept. of Pathology and Temple University, Philadelphia, PA.

Background: Flaxseed (FS) is a grain with antioxidant properties used as a nutritional supplement, although known for its usefulness in a variety of inflammatory pathologic conditions and cancer. Our group has investigated flaxseed in acute lung disease modeled in mice and confirmed protective properties by boosting antioxidant defenses in lung tissues. FS’s use in preventing or decreasing the adverse side-effects of thoracic X-ray radiation (XRT), the oxidative process of lung damage, has never been investigated. Methods: We evaluated mice fed either 10% FS or 0% control diets for 3 weeks prior to thoracic XRT. Irradiated mouse lungs were evaluated at 3 weeks post XRT for early pneumonitis and at 4 months for late, radiation-induced fibrosis. Results: Although dietary FS did not improve early lung inflammation, oxidative lung damage shown by malondialdehyde levels was significantly decreased (0.111±0.007 vs. 0.163±0.0.015 uM/g lung in 10% FS vs. 0%FS, respectively). This effect was associated with an abrogation of late lung fibrosis as evaluated quantitatively by lung hydroxyl-proline content (1.47±0.01 ug/ml hydroxy-proline per lung in 10% FS vs. 1.70±0.03 in 0%FS, representing a 10.5% vs. 39% increase from non-irradiated, age-matched control mice placed on the respective diets). This finding was confirmed histologically by Trichrome-blue staining. In addition, FS improved mouse survival rates in two separate experiments (65% vs. 40% and 93% vs. 66% for 10% FS vs. 0%FS respectively), although not significantly (p=0.06). Importantly, FS did not protect lung tumor growth from responding to radiation treatment. Conclusion: Dietary FS is protective against pulmonary fibrosis and oxidative lung damage and may be a useful, safe adjuvant therapy in lung cancer treatment.

Funded by: NIHR21, AICR and U. Penn Research Foundation (MCS).