Experimental lung tumors following specific intrabronchial application of chrysotile asbestos. Longitudinal light and electron microscopic investigations in rats.

Longitudinal light and electron microscopy investigations were previously carried out on Wistar rats to study the pathogenesis of pulmonary fibrosis due to asbestos. In the present study, the genesis of pulmonary carcinomas and pleural mesotheliomas have been investigated by light and electron microscopy on the same model after intrabronchial instillation of chrysotile B and benz(a)pyrene, as well as a combination of the two carcinogens. A single instillation of 1 mg chrysotile B with a fiber length between 0.05 and 0.2 micron in 0.1 ml tricaprylin by means of a polyvinyl catheter into the right lower lobe of the lung of 70 anesthetized 6-week-old Wistar rats caused pulmonary carcinomas or malignant pleural mesotheliomas in 18 animals (24%). The tumors occur at intervals between 12 and 31 months after the asbestos application. By electron microscopy, small asbestos fragments can be detected under the pleural mesothelium at the earliest 1 year after the intrabronchial application of chrysotile. A single combined instillation of 1 mg chrysotile and 0.5 mg benz(a)pyrene does not increase the tumor incidence. With simultaneous administration of these two substances, however, lung tumors arise very much earlier than in instillation of only one of the carcinogens. Thus, an adenocarcinoma was found in the lungs after 4.5 months, and a pleural mesothelioma was already found after 7.7 months. The intrabronchial instillation of benz(a)pyrene alone causes fewer lung tumors (tumor incidence 10%, interval between 13 and 33 months).