Therapeutic relationships between DNA synthesis and repair, membrane differentiation, and organ-specific immunotherapy in neuroblastoma.

The mouse neuroblastoma cell system (MNB) is of interest to both neurobiologists and cancer researchers because of its capacity to differentiate, with the consequent loss of some properties classically associated with malignancy. The effects of chemotherapeutic agents on MNB cells are variable; in general, cell cycle-specific agents will frequently induce differentiation, leaving viable surviving cells, while cell cycle nonspecific agents are toxic to both dividing and nondividing MNB cells. X-rays appear intermediate in that they are toxic to both cell populations, but survivors tend to resemble cells treated with cell cycle-specific drugs. Differentiated MNB cells apparently lose their capacity to repair some forms of DNA damage and this loss may be associated with their sensitivity to DNA damaging compounds. MNB cells are also susceptible to immunological lysis, particularly antibody-dependent cellular cytotoxicity. Integration of these diverse modes of MNB cell killing is of great interest because of the close resemblance of this murine tumor to human cancers in which cell differentiation is also partially membrane-mediated an indepth study of MNB cell surface receptors may have general relevance in the theoretical approach to cancer treatment.