Carcinogenesis From Inhaled (PuO2)-Pu-239 in Beagles: Evidence for Radiation Homeostasis at Low Doses?
From the early 1970s to the late 1980s, Pacific Northwest National Laboratory conducted life-span studies in beagle dogs on the biological effects of inhaled plutonium (239PuO2, 238PuO2, and 239Pu[NO3]4) to help predict risks associated with accidental intakes in workers. Years later, the purpose of the present follow-up study is to reassess the dose-response relationship for lung cancer induction in the 239PuO2 dogs compared to controls, with particular focus on the dose-response at low lung doses. A 239PuO2 aerosol (2.3 μm AMAD, 1.9 μm GSD) was administered to six groups of 20 young (18-month old) beagle dogs (10 males and 10 females) by inhalation at six different activity levels, as previously described in Laboratory reports. Control dogs were sham-exposed. In dose level 1, initial pulmonary lung depositions were 130 ± 48 Bq (3.5 ± 1.3 nCi), corresponding to 1 Bq g-1 lung tissue (0.029 ± 0.001 nCi g-1. Groups 2 through 6 received initial lung depositions (mean values) of 760, 2724, 10345, 37900, and 200000 Bq (22, 79, 300, 1100, and 5800 nCi) 239PuO2, respectively. For each dog, the absorbed dose to lungs was calculated from the initial lung burden and the final lung burden at time of death and lung mass, assuming a single, long-term retention function. Insoluble plutonium oxide exhibited long retention times in the lungs. Increased dose-dependent mortality due to lung cancer (bronchiolar-alveolar carcinoma, adenocarcinoma, epidermoid carcinoma) and radiation pneumonitis (highest exposures group) was observed in dogs exposed to 239PuO2. Calculated lung doses ranged from a few cGy in early-sacrificed dogs to 7764 cGy in dogs that experienced early deaths from radiation pneumonitis. Data were regrouped by lifetime lung dose and plotted as a function of lung tumor incidence. Lung tumor incidence in controls and zero-dose exposed dogs was 18% (5/28). However, no lung tumors were observed in 16 dogs with the lowest lung doses (8 to 22 cGy, mean 14.4 ± 7.6 cGy), and only one lung tumor was observed in 10 dogs with lung doses ranging from 27 to 48 cGy (mean 37.5 ± 10.9 cGy). By least-squares analysis, a quadratic function represented the overall dose-response (n = 137, r = 0.96) with no dose threshold. Reducing this function to three linear dose-response components, risk coefficients were calculated for each. The incidence of lung tumors at zero dose was significantly greater than the incidence at low dose (at the p ≤ 0.053 confidence level), suggesting a protective effect (radiation homeostasis) of alpha-particle radiation from 239PuO2. If a threshold for lung cancer incidence exists, it will be observed in the range 15 to 40 cGy.
- Research Organization:
- Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
- Sponsoring Organization:
- USDOE
- DOE Contract Number:
- AC05-76RL01830
- OSTI ID:
- 988618
- Report Number(s):
- PNNL-SA-66818; ST6001030; TRN: US201018%%578
- Journal Information:
- Health Physics, 99(3):357-362, Vol. 99, Issue 3; ISSN 0017-9078
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
99 GENERAL AND MISCELLANEOUS//MATHEMATICS, COMPUTING, AND INFORMATION SCIENCE
ACTIVITY LEVELS
BEAGLES
BIOLOGICAL EFFECTS
CARCINOGENESIS
DOSE-RESPONSE RELATIONSHIPS
HOMEOSTASIS
INDUCTION
INHALATION
LIFE SPAN
LUNGS
MORTALITY
NEOPLASMS
PLUTONIUM OXIDES
PNEUMONITIS
RADIATION DOSES
RADIATIONS
RETENTION
RETENTION FUNCTIONS
SINGLE INTAKE
PLUTONIUM DIOXIDE
RADIATION