The Bioassay of Carcinogenesis: Effects on the Epithelial Cell Complement of Rat Tracheae Maintained in vitro
The effects on the epithelium of suckling rat tracheae in organ cultures of three polycyclic hydrocarbons, 7,12-dimethylben(a)anthracene and benzo(a)pyrene which are carcinogenic and pyrene which is not carcinogenic, of diethylnitrosamine and of cigarette smoke condensates prepared from two types of cigarettes were studied. The changes found in the epithelial cell complement were analyzed by differential cell counts which revealed the relative numbers of undifferentiated, normally differentiated and abnormally differentiated cells present. It was found that the same general pattern of change, involving a reduction in the proportion of differentiated cells at low concentrations of test material and an increasing proportion of abnormally differentiated cells at higher concentrations was found with all the carcinogens and the cigarette smoke condensates but not with the noncarcinogen. Some evidence suggesting that this constant pattern of change was induced in a different manner by different materials was found. The total cell number per unit length of epithelium was also recorded and it was found that all of the active materials caused an increase in total cell number except in the case of 7,12-dimethylben(a)anthracene which was markedly toxic and reduced cell number at relatively low concentrations. Differences in the magnitude of effect on the level of differentiation in the epithelium between the two cigarette smoke condensates were found and were similar in extent to differences which have been found in skin painting experiments. It is suggested that the method has potential appplication as a predictive bioassay for carcinogenic materials.
KeywordsOrgan Culture Undifferentiated Cell Total Cell Number Squamous Metaplasia Differential Cell Count
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