Measurement of Epidermoid Carcinoma Development Induced in the Lungs of Rats by 3-Methylcholanthrene-Containing Beeswax Pellets

Summary

We have examined a method of inducing epidermoid carcinoma of the lung that has advantages in screening potential pulmonary carcinogens and in examining at a focal point other factors that might affect carcinogenesis. A mixture of equal volumes of beeswax and tricaprylin was heated to 76°C and injected by open thoracotomy, at a dose of 0.05 ml, directly into the lower peripheral segment ofthe left lung of female Osborne-Mendel rats. Pulmonary responseduring 1 year of observation was a bland granulomatous infiltrate limited to the surface of the solidified pellets. When graded doses of 0.005-0.5 mg 3-methylcholanthrene were added to the pellets, a series of metaplastic and neoplastic epithelial lesions developed at the pellet surface. These changes could be categorized in a progressive series as keratinizing squamous metaplasia, keratinizing squamous dysplasia with localized extension, overt squamouscell carcinoma, and undifferentiated neoplasms. With all doses of the carcinogen, squamous metaplasia developed before 17 weeks at frequencies directly related to dose. Subsequently, the carcinomas developed from this pool of metaplastic lesions at rates and frequencies also directly related to dose, but not in direct proportion to the frequency of the initial metaplastic lesions. Since the ratio of metaplasia to carcinoma was lower with low doses than with high doses of carcinogen, it followsthat the initial metaplastic lesion cannot be used as a direct index of carcinogenicity.