a drug that blocks cell division.
The mechanism by which cytostatic agents suppress certain stages of cell division vary. For example, alkylating agents, such as embichin (mechlorethamine hydrochloride) and cyclophosphamide, react directly with DNA. Antimetabolites suppress metabolism in the cells and compete with normal metabolites, the precursors of nucleic acids; they include the folic acid antagonist methotrexate, the purine antagonists 6-mercaptopurine and thioguanine, and the pyrimidine antagonists 5-fluorouracil and cytosine arabinoside. Some antitumor antibiotics, such as chrysomallin and rubomycin, block nucleic acid synthesis, while alkaloids of plant origin, such as vincristine, prevent the disjunction of chromosomes during cell division. The final effect of cytostatic agents, the selective suppression of dividing cells, is comparable to the biological effects of ionizing radiation, although the mechanisms of cytostatic action differ.
Many cytostatic agents are capable of either suppressing tumor growth or inhibiting the reproduction of normal cells of specific tissues. For example, Myelosan can inhibit parent hematopoietic cells of bone marrow, but it has virtually no effect on lymph cells or intestinal epithelial cells. Cyclophosphamide, on the other hand, can inhibit lymphatic cells, and therefore it is used to suppress immune reactions, while Myelosan is effective in the treatment of certain tumors arising from hematopoietic bone-marrow cells, as, for example, in chronic myelocytic leukemia.
The ability of cytostatic agents to suppress cell reproduction has made these drugs useful in the chemotherapy of malignant tumors (seeANTINEOPLASTIC). Since malignant tumors contain sets of different cells, which differ in the rate of reproduction and in metabolic characteristics, they are usually treated with several cytostatic agents simultaneously, thereby preventing recurrences because of the reproduction of cells resistant to a particular drug. The combined use of several cytostatic agents has helped prolong the lives of, and sometimes even cured, persons suffering from Hodgkin’s disease, acute lymphoblastic leukemia, choriocarcinoma, and some other types of tumors.
Some cytostatic agents are used as immunosuppressive agents, in autoimmune diseases to inhibit immunological action caused by the production of antibodies against the body’s own tissues and in transplantation to prevent the formation of antibodies against the transplanted organ. This effect of cytostatic agents is due to the cessation of the division of the corresponding immunocompetent lymphatic cells. Fairly large doses of cytostatic agents eventually lead to cytostatic disease, characterized by the inhibition of hematopoiesis and by the formation of lesions in the gastrointestinal tract, on the skin, and in liver cells. This necessitates the limitation of therapeutic doses of the drugs, especially in the treatment of tumors.
REFERENCESPetrov, R. V., and V. M. Man’ko. Immunodepressory (Spravochnik). Moscow, 1971.
Sigidin, Ia. A. Mekhanizmy lechebnogo deistviia antirevmaticheskikh sredstv. Moscow, 1972.
Novoe v gematologii. Edited by A. I. Vorob’ev and Iu. I. Lorie. Moscow, 1974.
Mashkovskii, M. D. Lekarstvennye sredstva, 7th ed., vol. 2. Moscow, 1972.
A. I. VOROB’EV and E. G. BRAGINA