Recovery of normal hematopoietic tissue and tumor following chemotherapeutic injury from cyclophosphamide (CTX): comparative analysis of biochemical and clinical techniques

Simultaneous alterations in the incorporation of 3H-thymidine (3H-TdR) into DNA are induced by CTX in normal host target tissues and L1210 ascites tumor. The timing of suppression and recovery of these nucleoside incorporation alterations was similar at the three CTX doses studied, but some evidence for a dose-response effect was seen as the magnitude of suppression of DNA synthesis increased with increasing dosage. A differential pattern of suppression and recovery of 3H-TdR incorporation in malignant and normal host tissues was observed. The pattern of suppression and recovery of the peripheral white blood count and bone marrow (BM) cellularity, two frequently studied clinical parameters of hematopoietic recovery, were out of phase with the recovery of BM-DNA synthesis and failed to accurately reflect the sensitivity of the BM to subsequent chemotherapeutic injury. In contrast, drug schedules based on the differential recovery patterns of the host tissues and tumor, reflected by their 3H-TdR incorporation into DNA, both reduced toxicity to normal mice and increased the survival of tumor-bearing animals.