Multisystem stem cell failure after apparent recovery from alkylating agents
Botnick, L.E.; Hannon, E.C.; Hellman, S.
Cancer Research 38(7): 1942-1947
1978
ISSN/ISBN: 0008-5472 PMID: 657132 Document Number: 128793
Failure of cell renewal systems is rarely a cause of death in mammals since these systems have a proliferative capacity that exceeds the life span of the mammals. While permitting seemingly complete recovery, exposure to systemic chemotherapy may cause sufficient stem cell depletion to limit subsequent proliferative capacity. This hypothesis was tested in 8- to 12-wk-old male C3H/HeJ mice receiving 5-6 weekly i.p. injections of busulfan, L-phenylalanine mustard or cyclophosphamide. Mice treated with busulfan demonstrated permanent damage in bone marrow proliferative capacity when tested by serial transplantation and endogenous spleen colony formation for as long as 95 wk after drug administration the last time tested. These mice also exhibited a decreased antibody response to primary immunization with sheep erythrocytes, early graying of their fur and an increased incidence of cataract formation. Mice treated with L-phenylalanine mustard demonstrated a moderate defect in hematopoietic proliferation, showed a depressed immunological response and also developed a significantly higher incidence of leukemia and Harderian gland tumors. Although cyclophosphamide-treated mice do not show a hematopoietic defect, early graying of fur and an impaired immunological response to sheep erythrocytes were noted. These results support the theory that reserve cells of renewal tissues have limited proliferative capacity. With the increasing role of adjuvant therapy in cancer management, one must be concerned with the risk of developing late complications secondary to failure of cell renewal tissues.