Experimental Induction of Epidermoid Carcinoma in the Lungs of Rats by Cigarette Smoke Condensate

Abstract

Epidermoid carcinomas and preneoplastic lesions characterized by keratinizing squamous metaplasia were induced in the lungs of female, Osborne-Mendel rats by direct injection into the lung of 0.05–0.10 ml warm, liquefied beeswax containing either crude cigarette smoke condensate (CSC) or the heptane soluble fraction (HSF) of this condensate. Control pellets containing beeswax and tricaprylin or beeswax and either anthracene, unburned cigarette tobacco, or cigarette ash were enveloped by nonreactive epithelial tissue in a mild granulation tissue stroma. Beeswax pellets containing either CSC or HSF were enveloped by metaplastic epithelium in 45 of 55 rats dying the 1st year after implantation. During the 2d year, 106 of the 303 remaining rats have died. Of these, 44 had metaplastic lesions and 31 had epidermoid carcinomas at the pellet site. No dose-response relationship was noted over the relatively narrow range of 12–72 mg HSF used. The consistently high incidence of neoplasms induced by the condensate of <5 cigarettes indicates a highly sensitive system for study of the carcinogenicity of various CSC fractions. The metaplastic response, which develops within 4 weeks at the pellet site, may be of further value in the rapid assessment of tobacco products and other materials potentially carcinogenic for the lung.