polonium and Adenocarcinoma

This paper presents clinical, experimental, and epidemiologic evidence to help explain the rapidly increasing incidence of primary lung cancer, with recently observed reversal in leading cell type from squamous cell to adenocarcinoma. It postulates that this may be due to changes in modern cigarettes, with or without filters, which allow inhalation of increased amounts of radioactive lead and polonium and decreased amounts of benzopyrene. This hypothesis is based upon measurements of increased concentrations of radioactive polonium in the lungs of cigarette smokers, in modern tobaccos grown since 1950, and in high-phosphate fertilizers used for tobacco farming in industrialized countries. Critical support for this thesis is based upon experimental animal studies in which lung cancers that resemble adenocarcinomas are induced with as little as 15 rads of radioactive polonium, equal to one fifth the dosage inhaled by cigarette smokers who average two packs a day during a 25-year period.

Topics: Adenocarcinoma; Alpha Particles; Animals; Benzopyrenes; Carcinoma, Squamous Cell; Cricetinae; Female; Fertilizers; Humans; Lead; Lung; Lung Neoplasms; Male; Neoplasms, Radiation-Induced; Nicotiana; Plants, Toxic; Polonium; Smoking; Tobacco Smoke Pollution

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

Topics: Adenocarcinoma; Alpha Particles; Animals; Cricetinae; Disease Models, Animal; Dose-Response Relationship, Radiation; Lung Neoplasms; Male; Mesocricetus; Neoplasms, Experimental; Neoplasms, Radiation-Induced; Polonium; Radiation Dosage

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

Benzo(a)pyrene and 210Po were administered both simultaneously and sequentially by intratracheal instillations to Syrian golden hamsters in experiments designed to identify any synergistic interactions between these carcinogens. Their effects were additive after simultaneous administration. A significant synergistic interaction between the two agents appeared to occur when benzo(a)pyrene exposure followed 4 months after 210Po exposure. Most of this effect could be ascribed, however, to a potentiating effect of subsequent 0.9% NaCl solution instillations on 210Po carcinogenesis. These results emphasize the fact that seemingly innocuous stimuli may significantly potentiate lung carcinogenesis. The implications of these findings in terms of the interactions between alpha-radiation and cigarette smoke in human populations are discussed.

Topics: Adenocarcinoma; Alpha Particles; Animals; Benzopyrenes; Carcinoma, Squamous Cell; Cocarcinogenesis; Cricetinae; Humans; Lung Neoplasms; Male; Mesocricetus; Neoplasms, Experimental; Neoplasms, Radiation-Induced; Polonium; Smoking; Sodium Chloride; Solutions

Lung cancers have been induced in 9 to 53 percent of hamsters given multiple intratracheal instillations of polonium-210 in amounts yielding lifetime exposures of 15 to 300 rads to the lungs. Cigarette smokers have previously been estimated to receive 20 rads to areas of the bronchial epithelium from deposited polonium-210. This finding thus supports the hypothesis that alpha radiation resulting from the polonium-210 or lead-210 present in cigarette smoke may be a significant causative factor in human lung cancer.

Topics: Adenocarcinoma; Alpha Particles; Animals; Carcinoma, Squamous Cell; Cricetinae; Disease Models, Animal; Humans; Lead; Lung Neoplasms; Neoplasms, Experimental; Neoplasms, Radiation-Induced; Nicotiana; Plants, Toxic; Plutonium; Polonium; Radiation Dosage; Radioisotopes; Smoke; Smoking

Several cell lines designated HLAC were derived from primary lung carcinomas induced in Syrian hamsters by polonium-210 or benzo[a]pyrene. Primary tumor nodules were initially transplanted into cheek pouches, and the tumors that grew were passed into tissue culture and into the cheek pouches of other hamsters for continued in vivo passage. By serial passage and cloning, cell lines were isolated with plating efficiencies of 20-50% in vitro and 10-25% when cultured directly from solid tumors. These cells formed adenocarcinomas in vivo. The radiosensitivities in vitro of HLAC-4 and HLAC-14 varied; observed D0 (the inverse of the slope of the exponential portion of the survival curve) values were 80 and 155 rads, respectively; n (the dose at which the exponential portion of the survival curve extrapolates to 100% survival) values were approximately 1.8. Survival curves obtained following in situ irradiation of 4- to 5-mm3 HLAC-4 tumors showed a D0 of 80 rads and an n of 7. Morphology and growth characteristics of two HLAC cell lines in vivo and in vitro were described.

Topics: Adenocarcinoma; Animals; Benzopyrenes; Cell Division; Cell Line; Cricetinae; Dose-Response Relationship, Radiation; Lung Neoplasms; Male; Neoplasm Transplantation; Neoplasms, Experimental; Neoplasms, Radiation-Induced; Polonium; Transplantation, Homologous

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

Topics: Adenocarcinoma; Animals; Autoradiography; Benzopyrenes; Carcinoma, Squamous Cell; Cricetinae; Freeze Drying; Intubation, Intratracheal; Iron; Lung; Lung Neoplasms; Male; Microscopy, Fluorescence; Microscopy, Ultraviolet; Neoplasms, Experimental; Neoplasms, Radiation-Induced; Polonium; Time Factors

Topics: Adenocarcinoma; Adenoma; Adrenal Gland Neoplasms; Animals; Carcinoma, Squamous Cell; Dogs; Female; Kidney Neoplasms; Liver Neoplasms; Mammary Neoplasms, Experimental; Neoplasms, Radiation-Induced; Neutrons; Ovarian Neoplasms; Pancreatic Neoplasms; Parathyroid Neoplasms; Polonium; Skin Neoplasms; Thyroid Neoplasms; Urinary Bladder Neoplasms