Radiation effects in the lung.

Abstract

This article outlines the principles of radiobiology that can explain the time of onset, duration, and severity of the complex reactions of the lung to ionizing radiation. These reactions have been assayed biochemically, cell kinetically, physiologically, and pathologically. Clinical and experimental data are used to describe the acute and late reactions of the lung to both external and internal radiation including pneumonitis, fibrosis and carcinogenesis. Acute radiation pneumonitis, which can be fatal, develops in both humans and animals within 6 months of exposure to doses greater than or equal to 8 Gy of low LET radiation. It is divisible into a latent period lasting up to 4 weeks; an exudative phase (3-8 weeks) and with an acute pneumonitic phase between 2 and 6 months. The latter is an inflammatory reaction with intra-alveolar and septal edema accompanied by epithelial and endothelial desquamation. The critical role of type II pneumonocytes is discussed. One favored hypothesis suggests that the primary response of the lung is an increase in microvascular permeability. The plasma proteins overwhelm the lymphatic and other drainage mechanisms and this elicits the secondary response of type II cell hyperplasia. This, in its turn, produces an excess of surfactant that ultimately causes the fall in compliance, abnormal gas exchange values, and even respiratory failure. The inflammatory early reaction may progress to chronic fibrosis. There is much evidence to suggest that pneumonitis is an epithelial reaction and some evidence to suggest that this early damage may not be predictive of late fibrosis. However, despite detailed work on collagen metabolism, the pathogenesis of radiation fibrosis remains unknown. The data on radiation-induced pulmonary cancer, both in man and experimental animals from both external and internal irradiation following the inhalation of both soluble and insoluble alpha and beta emitting radionuclides are reviewed. Emphasis is placed on the data showing that alpha emitters are at least an order of magnitude more hazardous than beta/gamma radiation and on recent data showing that the more homogeneous the irradiation of the lung, the greater is the carcinogenic hazard which contradicts the so-called "hot particle" theory.ImagesFIGURE 6.

Decreasing Irradiated Rat Lung Volume Changes Dose-Limiting Toxicity From Early to Late Effects

“…The radiation-induced lung pathologies -vascular damage, inflammation and fibrosisassessed in this study have been recognized before in animals as well as in patients (3,6,7,11,13,(15)(16)(17)(18). However, the impact on RILD and the exact dose-volume relations of these different pathologies have not been investigated before.…”

“…Next we assessed the level of known radiation-induced lung pathologies -vascular remodeling, pulmonary inflammation and fibrosis (3,6,7,9,(13)(14)(15)(16)(17)(18) -by scoring the histology of lung slides (Fig. 3).…”

Radiation-Induced Lung Cancers in Murine Models

“…Whether an exposure to radiation will result in primarily pulmonary fibrosis or increased cancer risk appears to be a function of dose, with a much smaller dose required for initiation of carcinogenesis [23]. A report authored by Williams et al provides an extensive guide for the selection of radiation induced fibrosis animals models, as well as models of other radiation-induced malignancies [8].…”

“…The C3H mouse appears to be the optimal choice IR-LC studies with its low spontaneous and moderate induction frequencies. Coggle and colleagues suggest that induction with thoracic irradiations be the preferred method for this strain [23] due to clinical relevance and reduced induction of other tumors in the animal, that could contribute to lethality or obfuscate a lung cancer centered investigation.…”

Soluble TNF-α Receptor I Encoded on Plasmid Vector and Its Application in Experimental Gene Therapy of Radiation-Induced Lung Fibrosis

“…Late adverse effects of radiotherapy are important clinical complications of radiation exposure during cancer treatment (Anscher 2005;Coggle et al 1986;Mehta 2005). Ionising irradiation can induce a cascade of events on tissue and cellular levels, which result in the early postradiation inflammatory reactions and late post-radiation fibrosis (Marks et al 2003;Trask et al 1985).…”