Carcinogens and the regeneration patterns after injury.

There is considerable evidence that carcinogens injure cells. Pullinger (10) described degenerative changes a n d believed that the injury was specific. Cramer and Stowell (2) found that carcinogens did not induce a proliferation of epithelial cells, but injured them and inhibited their mitotic activity for several days. The subsequent epithelial proliferation suggested to them a "protective response." Orr (8) described not only an initial atrophy of epithelium after the first application of a carcinogen, but changes in I;he collagen fibers of the dermis that he believed altered the blood supply of the epithelial cells and caused the malignant change. Wolbach (21) pointed out that cells in the subcutaneous tissues were destroyed about buried cholesterol pellets containing a carcinogen, and that encapsulation did not occur properly. Orr (9) confirmed these observations, and described the formation of fibrous tissue around paraffin pellets containing a carcinogen as "deficient in amount and failing to condense properly into a firm capsule." Stewart (18) wrote that the alteration about buried cholesterol pellets containing a carcinogen was a focal and diffuse chronic inflammatory change. If carcinogens produce neoplasms by causing cell injury, then to know what happens to the regeneration patterns that usually follow injury should help in understanding how tumors form. These regeneration patterns, epithelization and fibroplasia, are quite different in nature. Epithelization results from the amoeboid motion, proliferation, and maturation of preexisting epithelial cells; the process restores surfaces. Fibroplasia, on the other hand, which restores the continuity of the deeper structures of the body, consists of the proliferation and maturation of fibroblasts and the formation of reticulin and collagen. In fact, the phase of proliferation is brief, and the greater portion of the pattern is concerned with the elaboration of intercellular substances. This investigation will compare the changes that carcinogens cause in epithelium recovering from a traumatic injury and in intact epithelium. By observing fibroplasia about a buried carcinogen when a tumor develops and when a tumor fails to develop in (a) a susceptible animal and in (b) a naturally resistant animal, changes leading to the production of a sarcoma or to encapsulation should be discernible. Lastly, changes in fibroplasia about an embedded carcinogen when a sarcoma forms will be compared with those taking place in dermis when a epithelioma forms. METHODS