Chemotherapy in Experimental Cancer

Chemical agents being tested for their action on tumor growth are usually injected into animals with the hope that they will have a specific action on the malignant cell. While some chemicals have produced necrosis and regression of tumors, the effects often appear to be due to ischemia and cellular starvation resulting from vascular injury and thrombosis, rather than to a selective action of the chemical on the cell itself. Although evidence for the therapeutic value of heavy metals, particularly lead, is contradictory, it may be said that some metals given in sufficiently large doses produce vascular impairment, thrombosis, and necrosis, as was shown by Izar and Basile (1912) for colloidal sulphur, Weil (1913) for copper, and Wood (1926) for lead. Wood states that thrombi are abundantly present in tumor capillaries twenty-four hours after the injection of colloidal lead into rats bearing sarcoma 39. In order to produce extensive injury of the larger vessels and marked destruction of the tumor, the dosage must, however, approach the lethal. The great toxicity of the heavy metals in effective doses seems to be the chief obstacle to their more extensive use.' Since the inhibitory effect of certain heavy metals would seem ascribable to the results of thrombosis (Cruickshank, 1931), attempts to enhance thrombus formation by the addition of clot-forming agents are warranted. In combination with active thrombogenic agents, such as thrombin, thromboplastin, or cephalin, the dose of the toxic metal might be reduced to a level effective and safe. As rapidly growing endothelial cells of tumor vessels are more susceptible to traumatization than are cells of mature vessels, the site of thrombus formation might be localized to areas of rapid growth. Accordingly, attempts were made to establish intratumoralclots by first traumatizing the tumoral vessels with a heavy metal and later injecting thrombogenic agents. I t should be pointed out that attempts to devise methods by which the coagulability of blood can be controlled have a practical bearing in application to pathological conditions other than cancer in which the blood balance is disturbed in the direction of an increased or decreased coagulability.