Recovery of normal hematopoietic tissue and tumor following
chemotherapeutic injury from cyclophosphamide (CTX): comparative analysis
of biochemical and clinical techniques
SH Rosenoff, F Bostick and RC Young
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.
Volume 45,
Issue 4,
pp. 465-475,
04/01/1975
Copyright © 1975 by The American Society of Hematology
