Chronic cigarette smoke exposure increases the pulmonary retention and radiation dose of 239Pu inhaled as 239PuO2 by F344 rats

As a portion of a study to examine how chronic cigarette smoke exposure might alter the risk of lung tumors from inhaled (PuO2)-Pu-239, 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 (PuO2)-Pu-239, 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), 5 d wk(-1), for 30 mo. A single, pernasal, acute exposure to (PuO2)-Pu-239, 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 (PuO2)-Pu-239, exposure deposited less Pu-239 in the lung than did controls. Except for male rats exposed to LCS, exposure to smoke retarded the clearance of Pu-239 from the lung compared to control rats through study termination at 870 d after (PuO2)-Pu-239, 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 (PuO2)-Pu-239, 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 (PuO2)-Pu-239, and LCS or (PuO2)-Pu-239 and HCS, respectively.