PARENT SESSION
1:30 PM to 3:30 PM
Sunday, April 21, 2002
Poster Session 6 Normal Tissue Biology II
Room: Nevada Exhibition Center
(P11-102) A new paradigm of radiation-induced lung injury and mechanisms for intervention.
Vujaskovic, Zeljko*,1, Rabbani, Zahid1, Batinic-Haberle, Ines2, Samulski, Thaddeus1, Dewhirst, Mark1, Anscher, Mitchell, 1 Department of Radiation Oncology, Durham, NC2 Department of Biochemistry, Durham, NC
ABSTRACT-
The risk of unacceptable radiation-induced lung injury remains a significant limiting factor in the current treatment of the tumors involving the thoracic region. Despite advances in normal tissue radiobiology, demonstrating that ionizing radiation triggers a cascade of genetic and molecular events that proceed during a latent period of pulmonary injury, it is still unclear how this prolonged response to injury can be sustained for months to years after irradiation. Furthermore, the development of appropriate interventional approaches to prevent/ameliorate radiation-induced late normal tissue injury remains limited. In our rat studies, using 28 Gy single does of right hemithoracic radiation, we have found hypoxia to be associated with development of radiation-induced lung injury. It appears early, in macrophages, prior to the overt onset of any histologic or symptomatic evidence of injury and is more evident at the time of fibrosis, which is mixed with exuberant angiogenesis and extensive macrophage infiltration. Focal hypoxia in regions of macrophage accumulation, suggest that the mechanism responsible is high oxygen consumption, as would occur with creation of reactive oxygen species (ROS). ROS and hypoxia are likely to further stimulate the profibrogenic and proangiogenic pathways. Hypoxia therefore continuously perpetuates non-healing tissue response leading consequently to chronic radiation injury. To modified this effect, we have established that daily administration of superoxide dismutase (SOD) mimetic MnTE-2PyP (6 mg/kg ip) during the week surrounding a single dose of radiation can reduce radiation-induced lung damage. Targeting ROS in the initial phase of injury ( as we have done using strong antioxidant MnTE-2PyP) or during the hypoxia ROS generated period might be an effective way to modulate radiation-induced lung damage.
KEYWORDS: radiation-induced lung injury, hypoxia, SOD mimetic