polonium and Hyperplasia

Syrian Golden hamsters received 8 weekly intratracheal instillations of 0.2 microCi of the alpha-emitting isotope Po210 while being exposed to an atmosphere of 65% oxygen in the inspired air. Three months later, 42% of the animals had poorly differentiated lung carcinomas. On the other hand, no lung tumors were found in hamsters that received intratracheal instillations of Po210 and were kept in air. It is concluded that diffuse cell hyperplasia in the lung, caused by an inhalant, may constitute an additional risk factor in the pathogenesis of alpha-radiation induced lung cancer.

Topics: Animals; Cricetinae; Hyperplasia; Instillation, Drug; Lung; Lung Neoplasms; Male; Mesocricetus; Neoplasms, Radiation-Induced; Oxygen; Polonium

The role of cellular proliferation in a two-stage model of carcinogenesis in the hamster lung was investigated. Syrian golden hamsters were treated intratracheally with either one instillation of 0.2 microCi of 210Po (Po-0 group), seven weekly instillations of BP (0-BP group), or 0.2 microCi 210Po followed 15 weeks later by either seven instillations of 0.9% NaCl solution (Po-Sal group) or seven instillations of BP (Po-BP group). All BP instillations were 3 mg each of BP:ferric oxide (1:1, w/w) carrier particles). Serial sacrifices were performed for up to 85 weeks. Two hr before sacrifice, each animal was given i.p. injections of 200 microCi of [3H]thymidine. Glycol methacrylate section autoradiographs (1 micrometer) were prepared. Labeling indices in the alveolar region, labeling of terminal bronchiolar cells, and morphological changes were examined. Equal numbers of Po-Sal and Po-BP animals developed lung tumors. No tumors were found in Po-0 or 0-BP animals. Tumor development was preceded by the appearance of hyperplastic areas of bronchiolar-type cells in the alveolar region and by changes in morphology of bronchiolar cells. Labeling indices in the alveolar region of the treated groups were slightly increased relative to untreated controls. Labeling of terminal bronchiolar cells was highest in the Po-BP and 0-BP groups and was associated with much inflammation. A single 0.9% NaCl solution instillation also increased proliferation of bronchiolar cells. We conclude that 0.9% NaCl solution instillations may potentiate carcinogenesis in the hamster lung by acting as a nonspecific stimulus to proliferation; in addition, we conclude that not all hyperplasia progresses on to form lung tumors in the Po-BP and Po-Sal groups.

Topics: Animals; Benzopyrenes; Cell Division; Cricetinae; Epithelium; Ferric Compounds; Hyperplasia; Lung; Lung Neoplasms; Male; Mesocricetus; Neoplasms, Experimental; Polonium; Sodium Chloride

The present series of experiments was carried out in order to see what role pre-existing localized fibrosis plays in carcinogenesis of the lung. Hemorrhagic infarction was produced in the lung of 180 male Wistar rats by injecting 0.05 ml of hexachlorotetrafluorobutane into the tail vein. This resulted in localized fibrosis in the lung 3 months later. One hundred and fiften rats were alive 3 months after administration of the chemical. Of these animals, 30 were given no further treatment (control). The remaining 85 rats were given intratracheal instillation of 0.2 microCi of polonium-210 once a week, a total of 15 times. It was subsequently found that lung carcinoma was induced in close proximity to the localized pulmonary fibrosis in 3 of 26 rats (11.5%) during the period from completion of the 15 weekly administrations of polonium-210 until the end of this experiment (21 months after the 1st instillation of polonium-210). Polonium-210 was found to be deposited in the fibrous thickening of the alveolus around the subpleural fibrotic lesion, bronchial epithelium, and peribronchial lymph apparati at the initial period of administration of polonium-210, but during the period of pulmonary carcinogenesis, it was deposited in the localized fibrotic lesion in the lung and in a few cancer cells. This suggests that polonium-210 deposited in the pulmonary fibrotic lesion remains there over a long period of time, indicating a reduced clearance ability at this site.

Topics: Adenocarcinoma; Adenocarcinoma, Papillary; Animals; Carcinoma, Squamous Cell; Hyperplasia; Lung Neoplasms; Male; Neoplasms, Experimental; Neoplasms, Radiation-Induced; Polonium; Pulmonary Fibrosis; Rats

The pathogenesis of 210Po-induced tumors in the peripheral lung of Syrian golden hamsters has been studied in a serial sacrifice experiment utilizing both plastic (glycol methacrylate) and routine paraffin embedding procedures for lung sections. A rapid progression from hyperplasia of bronchiolar-type cells that appear in the alveolar region to malignant tumors was documented. Tumors began appearing as early as 15 weeks after the first intratracheal instillation of 210Po.

Topics: Adenocarcinoma; Animals; Carcinoma, Squamous Cell; Cricetinae; Hyperplasia; Lung Neoplasms; Male; Mesocricetus; Neoplasms, Experimental; Neoplasms, Radiation-Induced; Polonium; Precancerous Conditions; Time Factors

Topics: Adenocarcinoma; Animals; Benzopyrenes; Bronchial Neoplasms; Carcinogens; Carcinoma; Carcinoma, Squamous Cell; Cricetinae; Dose-Response Relationship, Drug; Dose-Response Relationship, Radiation; Female; Hyperplasia; Intubation, Intratracheal; Lung Neoplasms; Male; Neoplasms, Experimental; Neoplasms, Radiation-Induced; Papilloma; Polonium; Respiratory Tract Neoplasms; Time Factors; Tracheal Neoplasms