Lung damage following bone marrow transplantation. II. The contribution of cyclophosphamide
The effect of high-dose cyclophosphamide (Cy), either alone or in combination with irradiation, upon the development of interstitial pneumonitis (IP) after bone marrow transplantation (BMT) was investigated in a Brown Norway rat model. The parameters that were examined included ventilation rate, mortality, and histopathology. No damage to the lungs was observed in rats given Cy alone in supralethal dosages plus BMT, and mortality resulted from severe aplasia of hemopoietic and lymphoid tissues with multifocal hemorrhages, secondary infections, and sepsis. Two separate periods of mortality were observed within the first 180 days following whole thorax irradiation with a high dose rate (HDR; 0.8 Gy/min) or a low dose rate (LDR; 0.05 Gy/min). The addition of Cy prior to irradiation resulted in an increased mortality in the first period (before day 100) in all experimental groups. The influence of Cy on mortality at 180 days however, was different for the HDR and LDR experiments. The LD50-180 after HDR irradiation, dose range 8 to 18 Gy, was not significantly altered by the addition of Cy (100 mg/kg) 1 day prior to irradiation, whereas Cy (100 mg/kg) 1 day prior to LDR irradiation, dose range: 16 to 24 Gy, caused an enhancement of radiation damage with a decrease of the LD50-180 by 1.33 Gy. The dose modification factor (DMF) was 1.07. This enhancement was no longer significant after splitting up the dose of Cy in two dosages of 50 mg/kg given on 2 consecutive days prior to irradiation with a LDR. The extrapolation of the data in this rat model to available dose-response curves on IP after BMT and radiation pneumonitis in humans, implied that non-infectious IP is a radiation pneumonitis that is only slightly enhanced by Cy.
- Research Organization:
- Radiobiological Institute TNO, Rijswijk, The Netherlands
- OSTI ID:
- 6018835
- Journal Information:
- Int. J. Radiat. Oncol., Biol. Phys.; (United States), Vol. 13:10
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
ANTINEOPLASTIC DRUGS
RADIOSENSITIVITY EFFECTS
BONE MARROW
TRANSPLANTS
LUNGS
BIOLOGICAL RADIATION EFFECTS
PNEUMONITIS
RADIOINDUCTION
BIOLOGICAL MODELS
CHEST
FRACTIONATED IRRADIATION
MORTALITY
RATS
ANIMAL TISSUES
ANIMALS
BIOLOGICAL EFFECTS
BODY
BODY AREAS
DRUGS
HEMATOPOIETIC SYSTEM
IRRADIATION
MAMMALS
ORGANS
RADIATION EFFECTS
RESPIRATORY SYSTEM
RODENTS
TISSUES
VERTEBRATES
560152* - Radiation Effects on Animals- Animals