Summary.-Mice were exposed to plutonium dioxide (PuO 2) aerosols 2 weeks before or after urethane injection. Both exposures reduced the number and size of adenomas. The incidence of arrested metaphases showed no consistently significant differences between plutonium-exposed and mock-exposed animals.The results are discussed in relation to recent electron microscopic evidence of degenerative changes in the type II epithelial cells of the mouse lung following PuO2 inhalation. It is concluded that damage at the cellular level may account for the observed reduction in growth of pulmonary adenomas in mice whose lungs contained plutonium particles.THE INCIDENCE of pulmonary adenomas in urethane-treated mice is decreased by large doses of whole-body X-irradiation (Foley and Cole, 1963;Bartlett, 1970). Inhalation of 239PuO 2 particles 2 weeks before urethane injection led to a significant decrease in tumour incidence (Brightwell and Heppleston, 1973). The proliferative response in the tumours has now been examined as well as the effect of Pu inhalation after uretbane administration.
MATERIALS AND METHODSRandom-bred, male A2G mice 4 to 7 mnonths old were used. Animals were divided into 4 age-matched groups, each of wrhich contained 57 animals in Experiment 1 and 26 in Experiment 2, the treatments being as follows: Experiment 1.-(a) Plutonium inhalation followed by urethane (PU); (b) plutonium inhalation followed by saline (PS); (c) mock inhalation followed by urethane (MU); (d) mock inhalation followed by saline (MS). Experiment 2.-(a) Urethane followed by plutonium inhalation (UP); (b) saline followed by plutonium inhalation (SP); (c) urethane followed by mock inhalation (UM); (d) saline followed by mock inhalation (SM).An aerosol of 239PuO2 was generated by an exploding-wire technique, and inhalation took place in a specially devised chamber with the mice partially enclosed in glass tubes (Brightwell and Carter, 1976). The average lung deposit was estimated to be 925 Bq (25 nCi). Mock exposure of inice similarly enclosed in glass tubes -was carried out in the laboratory atmosphere. Urethane (1 mg/g body weight) or saline was injected i.p. 2 weeks before or after inhalation exposure. Mice also received an i.p. injection of vinblastine sulphate (4 ,tg/g body weight) 4 h and [3H] thymidine (1-85 x 104 Bq [0-5 jrCil/g body weight) 1 h before death.Groups of 6 or 7 mice were killed by cervical dislocation at intervals up to 37 weeks after urethane or saline injection, the animals remaining healthy throughout. The lungs were fixed in Carnoy's fluid and tumours on the surfaces of both lungs were counted and measured using a dissecting microscope. From the left lung, 5-,tm paraffin sections were either stained by the periodic acid-Schiff/haematoxylin method or used for autoradiography with Kodak AR 10 stripping film. The mitotic incidence (MI) following metaphase arrest for a nominal 4 h and the labelling incidence (LI) after 1 h were estimated in individual tumours. Unless stated otherwise, statistical significance was determ...