title: Late-occurring pulmonary pathologies following inhalation of mixed oxide (uranium + plutonium oxide) aerosol in the rat.
abstract: Accidental exposure by inhalation to alpha-emitting particles from mixed oxide (MOX: uranium and plutonium oxide) fuels is a potential long-term health risk to workers in nuclear fuel fabrication plants. For MOX fuels, the risk of lung cancer development may be different from that assigned to individual components (plutonium, uranium) given different physico-chemical characteristics. The objective of this study was to investigate late effects in rat lungs following inhalation of MOX aerosols of similar particle size containing 2.5 or 7.1% plutonium. Conscious rats were exposed to MOX aerosols and kept for their entire lifespan. Different initial lung burdens (ILBs) were obtained using different amounts of MOX. Lung total alpha activity was determined by external counting and at autopsy for total lung dose calculation. Fixed lung tissue was used for anatomopathological, autoradiographical, and immunohistochemical analyses. Inhalation of MOX at ILBs ranging from 1-20 kBq resulted in lung pathologies (90% of rats) including fibrosis (70%) and malignant lung tumors (45%). High ILBs (4-20 kBq) resulted in reduced survival time (N = 102; p < 0.05) frequently associated with lung fibrosis. Malignant tumor incidence increased linearly with dose (up to 60 Gy) with a risk of 1-1.6% Gy for MOX, similar to results for industrial plutonium oxide alone (1.9% Gy). Staining with antibodies against Surfactant Protein-C, Thyroid Transcription Factor-1, or Oct-4 showed differential labeling of tumor types. In conclusion, late effects following MOX inhalation result in similar risk for development of lung tumors as compared with industrial plutonium oxide.
authors.affiliation: CEA/DSV/iRCM/Laboratoire de RadioToxicologie, Bruyeres le Châtel, 91297 ARPAJON France. nina.griffiths@cea.fr
authors.forename: N M
authors.initials: NM
authors.lastname: Griffiths
authors.forename: A
authors.initials: A
authors.lastname: Van der Meeren
authors.forename: P
authors.initials: P
authors.lastname: Fritsch
authors.forename: M-C
authors.initials: MC
authors.lastname: Abram
authors.forename: J-F
authors.initials: JF
authors.lastname: Bernaudin
authors.forename: J L
authors.initials: JL
authors.lastname: Poncy
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols / Q000008:administration & dosage / Q000737:chemistry* / Q000633:toxicity*; D000818:Animals; D001822:Body Burden; D004307:Dose-Response Relationship, Radiation; D007150:Immunohistochemistry; D008103:Liver Cirrhosis / Q000139:chemically induced; D008168:Lung / Q000187:drug effects / Q000473:pathology* / Q000528:radiation effects*; D008175:Lung Neoplasms / Q000139:chemically induced / Q000473:pathology; D008297:Male; D011005:Plutonium / Q000008:administration & dosage* / Q000378:metabolism / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D017974:Uranium Compounds / Q000008:administration & dosage* / Q000378:metabolism / Q000633:toxicity*
chemical_list: D000336:Aerosols; D017974:Uranium Compounds; C026885:plutonium dioxide; D011005:Plutonium; C047385:uranium oxide