Occupational Cancer. Lung Cancer - A Lesson from Experiments - Pathogenesis of Lung Cancer as Viewed by the Researcher.
NIOSH 1980 Jun:27-30
The detection of the precursors of cancer cells was studied. Tracheas were transplanted from normal rats to isogenic hosts. After 3 to 4 weeks a pellet containing the test carcinogen was inserted into the transplant. The release rate was controlled by modifying the matrix of the pellet. The mucociliary epithelium soon changed and the graft was eventually destroyed by the invading cancer. While the site of self renewal and proliferation in the hyperplastic epithelium was the basal layer, the proliferation in dysplastic lesion (DL) also occurred in suprabasal layers. DL also contained cells with high nuclear cytoplasmic ratios. The fate of the induced DL was determined by exposing tracheal transplants to 165 micrograms (microg) of dimethylbenzanthracene (57976) (DMBA) for 4 weeks and 2.5 years. The long period cumulative tumor incidence was 10 percent. Four months after the cessation of carcinogen exposure the de-novo formation of DL was observed; thereafter the number of lesions decreased. The number of dysplasias was higher at any given time than the number of cancers, indicating that the majority of dysplasias never developed into cancer. When a noncarcinogenic dose of chrysotile (12001295) asbestos was inserted into tracheas 4 weeks after DMBA, there was no difference in the response at the high DMBA dose; however, at 25 and 50microg chrysotile fibers increased the expression of insult dramatically. The normal tracheal cells died after a few weeks in-vitro, while tracheal epithelium exposed to carcinogen continued to grow in-vitro for several years. Some of these cells became malignant after 200 to 500 days. If inoculated into an animal, they usually caused squamous cell carcinoma. Eight months after the exposure to low doses DMBA, 80 percent of all tracheas contained cells with neoplastic potential. The author concludes that there are many more cells with neoplastic potential in carcinogen exposed organs than the tumor response would suggest. The tumorigenic potential is expressed when permissive or promoting conditions prevail.
NIOSH-Author; NIOSH-Contract; Contract-210-79-0009; In-vivo-studies; In-vitro-studies; Laboratory-animals; Carcinogenesis; Polynuclear-aromatic-hydrocarbons; Asbestos-fibers; Synergism; Cancer-rates; Chronic-exposure;
Mixed Exposures; Work Environment and Workforce;
Occupational Safety and Health Symposia 1979, NIOSH, U.S. Department of Health and Human Services, Cincinnati, Ohio, DHHS (NIOSH) Publication No. 80-139