Modifying Effects of Preexisting Pulmonary Fibrosis on Biological Responses of Rats to Inhaled 239PuO2

Abstract

We investigated the modifying effects of preexisting, bleomycin-induced pulmonary fibrosis on the deposition, retention, and biological effects of inhaled 239PuO2 in the rat. Among rats exposed to similar airborne concentrations of 239PuO2, initial lung burdens of 239Pu per kilogram body mass were similar whether or not pulmonary fibrosis was present. However, clearance of 239Pu from the lungs was significantly decreased in the rats with preexisting pulmonary fibrosis. The incidence of lung lesions (epithelial hyperplasia, diffuse macrophage increases and aggregation, and loose and dense connective tissue) was significantly greater among rats with preexisting pulmonary fibrosis than among the exposed controls. Rats with preexisting fibrosis had shorter life spans than 239PuO2-exposed control rats. When groups of rats with similar alpha doses to the lungs were compared, the incidences of neoplastic lesions in the lung, the times to death of rats with lung neoplasms, and the risk of lung tumors per unit of alpha dose to the lungs in rats with or without pulmonary fibrosis were similar. The results of this study suggest that humans with uncomplicated pulmonary fibrosis may not be more sensitive to the carcinogenic effects of inhaled 239PuO2 than are individuals with normal lungs, assuming that the total alpha doses to the lungs are similar.

Low-Dose-Radiation Stimulated Natural Chemical and Biological Protection against Lung Cancer

“…This estimate is reasonably close to the value of 1.2 × 10 -4 ± 9.0 × 10 -5 mGy -1 previously reported for lung cancer in Mayak plutonium facility workers (Scott 2007b) based on Equation 1, which also includes the PROFAC. It is also close to the value of 1.0 × 10 -4 ± 5.0 × 10 -5 mGy -1 previously reported for lung cancer in F344/Crl rats that inhaled the alpha emitting aerosol 239 PuO 2 (Scott 2007b), based on studies conducted by Lundgren et al (1991). Using the lowest two dose groups reported by Muggenburg et al (1996) for 238 PuO 2 alpha-particle-induced lung cancer in beagle dogs, a slope parameter of 1.7 × 10 -4 ± 1.0 × 10 -5 mGy -1 was obtained and is consistent with the result obtained for rats and humans.…”

“…Alpha radiation administered alone is a potent inducer of lung cancer. Small doses (close to natural background radiation levels) can cause a significant increased incidence (Sanders et al 1976(Sanders et al , 1977Lundgren et al 1991;Sanders 2007). However, for combined exposure to low-dose alpha and low-dose gamma rays, the gamma-ray ANP could possibly prevent cancer induction by alpha radiation.…”

Rodent models of cardiopulmonary disease: their potential applicability in studies of air pollutant susceptibility.

“…Application of the bleomycin-induced fibrosis model to pollution research has been limited to studies of regional deposition and clearance of inhaled submicroscopic particles in the rat, mouse, and hamster (147,(157)(158)(159). In a rat model of bleomycin-induced fibrosis, we recently showed that modest mortality in response to ROFA instillation occurs only when the model exhibited active inflammation, though the dose of ROFA required to cause this response was rather high (25).…”

Biokinetics of nuclear fuel compounds and biological effects of nonuniform radiation.

“…McAnulty et al (137) observed dramatic increases in both synthesis and degradation rates of collagen in the mouse lung after exposure to 239PuO2, suggesting an extensive remodeling of the lung connective tissue matrix during development of fibrosis. Preexisting, bleomycininduced pulmonary fibrosis has been shown to decrease significantly the clearance of 239PuO2 in the rat lung (138). However, the risk of lung tumors in rats with or without existing pulmonary fibrosis were similar.…”