title: Chronic cigarette smoke exposure increases the pulmonary retention and radiation dose of 239Pu inhaled as 239PuO2 by F344 rats.
abstract: As a portion of a study to examine how chronic cigarette smoke exposure might alter the risk of lung tumors from inhaled 239puO2 in rats, the effects of smoke exposure on alpha-particle lung dosimetry over the life-span of exposed rats were determined. Male and female rats were exposed to inhaled 239PuO2 alone or in combination with cigarette smoke. Animals exposed to filtered air alone served as controls for the smoke exposure. Whole-body exposure to mainstream smoke diluted to concentrations of either 100 or 250 mg total particulate matter m(-3)(LCS or HCS, respectively) began at 6 wk of age and continued for 6 h d(-1), 5d wk(-1), for 30 mo. A single, pernasal, acute exposure to 239PuO2 was given to all rats (control, LCS and HCS) at 12 wk of age. Exposure to cigarette smoke caused decreased body weight gains in a concentration dependent manner. Lung-to-body weight ratios were increased in smoke-exposed rats. Rats exposed to cigarette smoke before the 239PuO2 exposure deposited less 239Pu in the lung than did controls. Except for male rats exposed to LCS, exposure to smoke retarded the clearance of 239Pu from the lung compared to control rats through study termination at 870 d after 239PuO2 exposure. Radiation doses to lungs were calculated by sex and by exposure group for rats on study for at least 360 d using modeled body weight changes, lung-to-body weight ratios, and standard dosimetric calculations. For both sexes, estimated lifetime radiation doses from the time of 239PuO2 exposure to death were 3.8 Gy, 4.4 Gy, or 6.7 Gy for the control, LCS, or HCS exposure groups, respectively. Assuming an approximately linear dose-response relationship between radiation dose and lung neoplasm incidence, approximate increases of 20% or 80% in tumor incidence over controls would be expected in rats exposed to 239PuO2 and LCS or 239PuO2 and HCS, respectively.
authors.affiliation: Inhalation Toxicology Laboratory, Lovelace Biomedical and Environmental Research Institute, Albuquerque, NM 87185, USA.
authors.forename: G L
authors.initials: GL
authors.lastname: Finch
authors.forename: D L
authors.initials: DL
authors.lastname: Lundgren
authors.forename: E B
authors.initials: EB
authors.lastname: Barr
authors.forename: B T
authors.initials: BT
authors.lastname: Chen
authors.forename: W C
authors.initials: WC
authors.lastname: Griffith
authors.forename: C H
authors.initials: CH
authors.lastname: Hobbs
authors.forename: M D
authors.initials: MD
authors.lastname: Hoover
authors.forename: K J
authors.initials: KJ
authors.lastname: Nikula
authors.forename: J L
authors.initials: JL
authors.lastname: Mauderly
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols; D000375:Aging / Q000502:physiology*; D000512:Alpha Particles; D000818:Animals; D001822:Body Burden; D005260:Female; D006801:Humans; D008168:Lung / Q000378:metabolism* / Q000473:pathology / Q000528:radiation effects*; D008297:Male; D009929:Organ Size; D011005:Plutonium / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051381:Rats; D011916:Rats, Inbred F344; D012727:Sex Characteristics; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*; D015430:Weight Gain
chemical_list: D000336:Aerosols; D014028:Tobacco Smoke Pollution; C026885:plutonium dioxide; D011005:Plutonium