183 Physica Medica - Vol. XVII, Supplement 1, 2001 Induction and Repair of HZE Induced Cytogenetic Damage A.L. Brooks 1 , S. Bao 2 , K. Rithidech 3 , W.B. Chrisler 4 , L.A. Couch 1 , L.A. Braby 5 1. Washington State University, Tricities, Richland, WA (USA) 2. US Transuranium and Uranium Registry, Washington State University, Richland, WA (USA) 3. New York University at Stony Brook, Stony Brook, NY (USA) 4. Pacific Northwest National Laboratory, Richland, WA (USA) 5. Texas A & M University, College Station, TX (USA) Abstract Wistar rats were exposed to high-mass, high energy (HZE) 56 Fe particles (1000 GeV/AMU) using the Alternating Gradient Synchrotron (AGS). The animals were sacrificed at 1-5 hours or after a 30-day recovery period. The frequency of micronuclei in the tracheal and the deep lung epithelial cells were evaluated. The relative effectiveness of 56 Fe, for the induction of initial chromosome damage in the form of micronuclei, was compared to damage produced in the same biological system exposed to other types of high and low-LET radiation. It was demonstrated that for animals sacrificed at short times after exposure, the tracheal and lung epithelial cells, the 56 Fe particles were 3.3 and 1.3 times as effective as 60 Co in production of micronuclei, respectively. The effectiveness was also compared to that for exposure to inhaled radon. With this comparison, the 56 Fe exposure of the tracheal epithelial cells and the lung epithelial cells were only 0.18 and 0.20 times as effective as radon in the production of the initial cytogenetic damage. It was suggested that the low relative effectiveness was related to potential for ‘wasted energy’ from the core of the 56 Fe particles. When the animals were sacrificed after 30 days, the slopes of the dose-response relationships, which reflect the remaining level of damage, decreased by a factor of 10 for both the tracheal and lung epithelial cells. In both cases, the slope of the dose-response lines were no longer significantly different from zero, and the r 2 values were very high. Lung epithelial cells, isolated from the animals sacrificed hours after exposure, were maintained in culture, and the micronuclei frequency evaluated after 4 and 6 subcultures. These cells were harvested at 24 and 36 days after the exposure. There was no dose-response detected in these cultures and no signs of genomic instability at either sample time. KEYWORDS: Micronuclei, HZE, respiratory epithelial cells, rats. 1. Introduction and Methods During prolonged space flights, there is a concern for the exposure to HZE particles and the potential for these particles to produce genomic instability [1] that could increase cancer risk [2]. Since most cancers originate in epithelial cells, it is important to study HZE induced changes in these cell types in vivo. The tracheal and lung epithelial cells were chosen for this study since the tracheal cells have been shown to be very resistant to the induction of cancer by high-LET radiation exposure, where as deep lung epithelial cells are sensitive [3]. Male Wistar rats, 4-6 weeks old were housed in AAALAC approved facilities at Brookhaven Natio- nal Laboratory and exposed to 1000 MeV/AMU 56 Fe particles at graded doses of 0, 20, 50, 100, and 200 cGy. They were sacrificed either within 1-5 hours after the exposure or after 30 days of in vivo recovery and the tracheal and deep lung epithelial cells were isolated and placed in short term culture. The cells were prepared for evaluation of micronu- clei using previously published methods [4]. Slides were coded and scored for the frequency of micro- nuclei in binucleated cells. Deep lung epithelial cells were further transferred in culture and were scored for micronuclei after passage 2, 4 and 6. 2. Results and Discussion The results of the cytogenetic evaluations have been submitted for publication. Briefly, the slope of the dose-response relationship for induction of micronu- clei/binucleated cell were 11.0 × 10 -4 and 12.0 × 10 –4 for the tracheal epithelial and deep lung epithelial cells, respectively. These were related to the frequen- cy of micronuclei induced following exposure to either the low-LET radiation from 60 Co gamma rays (4) or the high-LET alpha particles (5) from inhalation of radon. It was demonstrated that for the tracheal epi- thelial cells and the lung epithelial cells the 56 Fe par- ticles were 3.3 and 1.3 times as effective as 60 Co in production of micronuclei. The effectiveness for exposure to inhaled radon demonstrated that 56 Fe exposure of the tracheal epithelial cells and the lung epithelial cells were only 0.18 and 0.20 times as effective as radon in the production of the initial cytogenetic damage. It was suggested that the low relative effectiveness could be related to potential for ‘wasted energy’ from the core of the 56 Fe particles. Calculations indicated that up to 32 cells interact with the delta rays for every cell that is traversed by a primary particle. The data in the present paper sug- gest that much of the damage scored as micronuclei were induced by the delta rays. 1 st International Workshop on Space Radiation Research and 11 th Annual NASA Space Radiation Health Investigators’ Workshop Arona (Italy), May 27-31, 2000 In vivo studies