title: Carcinogenic interactions between a single inhalation of 239PuO2 and chronic exposure to cigarette smoke in rats.
abstract: Rats were exposed once by inhalation to plutonium-239 dioxide ((239)PuO(2)), resulting in chronic alpha-particle irradiation of the lung, and exposed chronically to cigarette smoke to examine carcinogenic interactions between the two exposures. F344 rats were exposed to (239)PuO(2) to achieve an initial lung burden of 0.5 kBq and then exposed 6 h/day, 5 days/week to cigarette smoke at 100 or 250 mg particulate matter/m(3) for up to 30 months. Exposure to cigarette smoke increased the cumulative radiation dose to lung by slowing the clearance of (239)PuO(2). (239)PuO(2) alone did not affect survival, but the higher cigarette smoke exposure shortened survival in females. Combined exposure to (239)PuO(2) and cigarette smoke acted synergistically to shorten survival in both genders. The combined effects of cigarette smoke and (239)PuO(2) were approximately additive for lung hyperplasia and adenomas but were strongly synergistic for carcinomas. Differences between observed incidences and incidences predicted by survival-adjusted models accounting for increased radiation dose revealed a substantial component of synergy for carcinomas above that attributable to the radiation dose effect. The synergy for malignant lung tumors is consistent with findings from uranium miners and nuclear weapons production workers. These results bolster confidence in the epidemiological findings and have implications for risk assessment.
authors.affiliation: Lovelace Respiratory Research Institute, Albuquerque, New Mexico 87108, USA. jmauderl@LRRI.org
authors.forename: Joe L
authors.initials: JL
authors.lastname: Mauderly
authors.forename: Steven K
authors.initials: SK
authors.lastname: Seilkop
authors.forename: Edward B
authors.initials: EB
authors.lastname: Barr
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Gigliotti
authors.forename: Fletcher F
authors.initials: FF
authors.lastname: Hahn
authors.forename: Charles H
authors.initials: CH
authors.lastname: Hobbs
authors.forename: Gregory L
authors.initials: GL
authors.lastname: Finch
mesh_terms: D000336:Aerosols; D000818:Animals; D003043:Cocarcinogenesis; D005260:Female; D019570:Inhalation Exposure; D008168:Lung / Q000473:pathology / Q000528:radiation effects; D008175:Lung Neoplasms / Q000209:etiology*; D008297:Male; D011005:Plutonium / Q000633:toxicity*; D011829:Radiation Dosage; D051381:Rats; D011916:Rats, Inbred F344; D012906:Smoke; D014026:Nicotiana
chemical_list: D000336:Aerosols; D012906:Smoke; D011005:Plutonium