Lung radioprotection by WR-2721 at low X-ray doses per fraction

The response of mouse lungs to single doses and ten fractionated irradiations has been tested using breathing rate and lethality as assays for damage. The radioprotective effect of 300 mg/kg WR-2721 has been determined for mice breathing air or 10% oxygen. The protection factor was assessed from dose response curves obtained at monthly intervals from 24 to 48 weeks. A low protection factor (1.2-1.4) was observed for single doses in air or 10% oxygen and also for ten fractions in air. Considerably more protection was seen with ten fractions in mice breathing the reduced oxygen concentration (protection factors of PF = 1.5-1.7). It is postulated that the low PF values normally reported for lung are due to the naturally high oxygen concentration in all cells in this tissue. A fraction of the cells becomes sufficiently hypoxic in 10% oxygen to be susceptible to WR-2721 radioprotection. This subpopulation can then be detected with small X-ray fractions (less than or equal to 5 Gy) but not with large single doses.