Comparison of single, fractionated and hyperfractionated irradiation on the development of normal tissue damage in rat lung.

The effect of fractionated thoracic irradiation on the development of normal tissue damage in rats was compared to that produced by single doses. Animals received a single dose of 15 Gy, 30 Gy in 10 daily fractions of 3 Gy each (fractionation), or 30 Gy in 30 fractions of 1 Gy each 3 times a day (hyperfractionation). The treatments produced minimal lethality since a total of only 6 animals died between days 273 and 475 after the initiation of treatment, with no difference in survival observed between the control and any of the 3 treated groups. Despite the lack of lethality, evidence of lung damage was obtained by histological examination. At times less than 180 days after treatment, the lungs of animals receiving a single dose of 15 Gy displayed more severe changes than did animals from either fractionation group. At longer times after treatment (days 261 and 475), the histological appearances within each group were changed, collagen deposits and fibrosis being the most significant observations. Animals that had received either single doses or fractionated doses had more of the pulmonary parenchyma involved than did animals that had received hyperfractionated doses. We conclude that, in the rat lung model, a total radiation dose of 30 Gy fractionated over 14 days produces no more acute lethality nor damage to lung tissue than does 15 Gy delivered as a single dose. However, long-term effects as evidenced by deposits of collagen and development of fibrosis are significantly reduced by hyperfractionation when compared to single doses and daily fractionation.