No Change in Repair Capacity of Mouse Lung Irradiated Three Months after a Single Dose of Cyclophosphamide

The repair capacity of mouse lung was determined at 3 months after a single i.p. injection of cyclophosphamide (Cy) at a maximally tolerated dose of 275 mg/kg. Mice were irradiated to the whole thorax only with 1,2,9, or 15 fractions of X-rays using doses/fraction ranging from 1.2 to 11 Gy. Breathing rate (breaths per minute), histology and pulmonary mortality were used to assess lung damage. Raw breathing rate data were converted to quanta! response data by scoring the number of mice in each dose group in each fractionation schedule with a breathing rate 13 times the breathing rate of control mice. Dose-response curves of mortality and the converted breathing rate data were constructed at 15 weeks after irradiation (approximately 28 weeks after drug treatment) fitted by logit analysis and 50% effective doses with 95% confidence limits obtained. Values of a/0 were obtained by using the direct analysis method of H. D. Thames et al (Int. J. Radiat. Biol., 49:999-1009,1986). The a/0 for mice given Cy 3 months before radiation was 3.69 Gy (95% confidence limits, 2.83, 4.69 Gy) and 3.06 Gy (95% confidence limits, 231, 3.99 Gy) for the lethality data and breathing rate data, respectively. These a/0 values are in good agreement with the previously published ranges of a/0 of 3 to 4 Gy for mouse lung not given Cy previously. Because the repair capacity of the target cells of a tissue govern the fractionation response and choice of fractionation regimen in clinical radiotherapy, these data indicate that the fractionation regimen used can remain the same as that used in non-drug-treated lungs when the lung is irradiated 3 months after exposure to Cy.