COMPARATIVE COCARCINOGENIC EFFECTS OF CROCIDOLITE ASBESTOS, HEMATITE, KAOLIN AND CARBON IN IMPLANTED TRACHEAL ORGAN CULTURES

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Abstract
The carcinogenicity of the polycyclic aromatic hydrocarbon (PAH), 3-methylcholanthrene (3 MC) in hamster tracheal tissues was examined after its adsorption on to four particulates–crocidolite asbestos, hematite, kaolin and carbon. After precipitation of 3 MC-coated particulates on the epithelial surface of the tracheal explants, the cultures were maintained for 4 weeks in vitro before either morphologic examination or implantation into syngeneic animals. Use of radiolabelled 3 MC made it possible to determine the relative amounts of the PAH adsorbed to and released from the particles with time. Tumours, the majority of which were carcinomas, appeared after exposure of organ cultures to 3 MC-coated particles, but not after exposure to particles alone. When total numbers of tumours (i.e. carcinomas, sarcomas and undifferentiated malignant tumours) were considered, the relative cocarcinogenicity of the dusts was crocidolite asbestos > hematite > kaolin > carbon. However, differences were not observed in the numbers of carcinomas induced by 3 MC-coated asbestos, hematite or kaolin. Relatively few carcinomas developed in animals exposed to carbon coated with 3 MC. Carcinogenicity was not related consistently to either the affinity of the particle for 3 MC or the elution of the hydrocarbon from the dust. For example, carbon adsorbed more 3 MC than the other particulates, but elution was minimal. Hematite released the greatest amount of PAH, whereas kaolin and asbestos eluted appreciably smaller quantities. Our data suggest that factors other than particle-enhanced availability of PAH are important in carcinogenesis in the respiratory tract. Alternative mechanisms of cocarcinogenesis by particulates include either cytotoxicity and the resultant augmentation of DNA synthesis or squamous metaplasia (or both).

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