Bleomycin and radiation-induced lung damage in mice

Abstract

Bleomycin-induced lung damage was assessed using both a functional end-point and mortality. The extent of lung damage was found to depend on the schedule, mode of administration and dose of the drug. Greater damage occurred following twice-weekly administration than when the same dose was given as a single injection. Intravenous administration resulted in greater damage than intraperitoneal administration. When bleomycin was given with thoracic irradiation lung damage occurred earlier and at lower radiation doses than with radiation alone. Similar responses were obtained whether bleomycin was given four weeks before, with or four weeks after irradiation. Thus although there was enhanced damage from the combined treatment, there was no evidence of a time-dependent interaction.

Enhancement of the Pneumotoxic Effect of Cadmium Acetate by Ionizing Radiation in the Rat

“…Enhancement ofpneumotoxicity has been reported for simultaneous treatment with some cytostatics (cyclophosphamide, bleomycin, etc.) and ionizing radiation (4)(5)(6)(7).…”

“…Most reports in the literature have been of in vitro studies, and the biological effects examined have largely pertained to the topics of carcinogenesis, mutagenesis, teratogenesis, and cellkilling rates (1)(2)(3). Other studies have modeled combined injury to tissues as observed in management of malignant disease with cytostatics and high-level doses of ionizing radiation (4)(5)(6)(7).…”

A survey of changing trends in modelling radiation lung injury in mice: bringing out the good, the bad, and the uncertain

“…77 In this context, there are a number of papers in which severe lung injury leading to mortality can be brought forward as well as enhanced to drastically shorten the latency period. This is typically seen experimentally following the combination of lung irradiation with cytotoxic drugs such as bleomycin and cyclophosphamide 78,79 as these drugs can elicit more immediate cell damage in the lung followed by stimulated proliferation and precipitation of radiation injury. A similar phenomenon has been reported following the pretreatment with butylated hydroxytoluene and only at a time when radiation was delivered at the time of type 2 pneumocyte but not endothelial cell proliferation.…”