Radiation-induced changes in collagen isotypes I, III, and IV in the lung of LAF1 mouse: effects of time, dose, and WR-2721.

Alterations in the amount and distribution of pulmonary connective tissue are commonly observed subsequent to thoracic radiotherapy. The extent to which these changes are important in the expression of radiation damage and its repair remains unclear. We have quantitated changes in the parenchymal levels of collagen types I, III, and IV in the lungs of LAF1 mice at intervals to 1 year, following doses of 0-14 Gy, 300 kV X rays, or 0-18 Gy in the presence of the radioprotective compound, WR-2721. The method of quantitation, which involves video image analysis of fluorescent antibody stained, cryostat tissue sections, provides both quantitative and morphological information for the three collagen isotypes. Type I collagen peaked in tissue content at 15 and 30 weeks postirradiation (p.i.), with transient return to control values 20-25 weeks p.i. Type III collagen peaked at 15 and 25 weeks p.i. and declined in tissue content at 20 and 30 weeks. Type IV peaked 15-20 weeks following irradiation, returned to control levels at 25 weeks, and reached a plateau above control values after 30 weeks. Fluctuations in collagen levels in the parenchyma were dose dependent but were not simultaneous, indicating a radiation response characterized by alpha-chain-specific regulation of collagen biosynthesis and breakdown. In general, WR-2721, which enhanced postirradiation survival (DMF, 1.3), reduced the magnitude and altered the timing of collagen fluctuations; again, the effects were type specific. The results clearly demonstrate that the postirradiation response of the connective tissue is dose dependent, is specific to each macromolecule, and involves both deposition and removal of extracellular matrix. These processes are independently influenced by the presence during irradiation of WR-2721.

Computed tomographic assessment of radiation induced damage in the lung of normal and WR 2721 protected LAF1 mice.

LAF1 mice were irradiated with single, graded doses of X rays to the thorax in the range of 0 to 14 Gy unprotected, or 0 to 18 Gy after injecting the radioprotective aminothiol compound, WR 2721. Computed tomographic (CT) scanning of the thorax was performed at intervals for a period of 42 weeks after irradiation. The gravimetric density was determined for both left and right lungs by averaging the CT numerical data within lung slices traced on a magnified video image of the thorax. Significant elevations in CT density occurred at post-irradiation times corresponding to pneumonitis and late phase, as evidenced by the pneumopathic decline in survival. The threshold dose yielding a significant increase in CT density in the pneumonitis phase was 11 Gy, a dose at which only 3% of the animals died. A single peak of increased CT density was observed for the pneumonitis phase for unprotected animals, whereas a transient return of CT density toward control values at 21-22 weeks produced two peaks from the WR 2721 treated group. The CT density of lung increased in a stepwise manner in the dose range of 11-14 Gy. For the isoeffect dose that produced equal animal survival (14 Gy and 18 Gy + WR 2721), the lung density increased by approximately 27% over control values for both treatments, suggesting that CT density is related to survival. Periodic computed tomographic analysis of the lungs of patients sustaining radiotherapy to large pulmonary fields may be of value in assessing the degree and progression of pulmonary complications.

Ectopic gonadotropin in a case of anaplastic large-cell carcinoma of the lung.

A case of ectopic gonadotropin production by a bronchogenic carcinoma is presented. Eleven similar cases have been previously reported. Urine gonadotropin titres appeared related to the size of the tumour mass since they decreased with response to treatment and increased when the tumour started progressing again. The hormone is most probably elaborated and secreted by the tumour cells.