Cell kinetics in spontaneous mammary tumors in inbred C3H/HeJ mice was studied in vitro methods at various intervals after treatment with 2.0 mg vincristine (VCR)/kg. Following acute doses, tumor volumes decreased approximately 30%, with tumor regrowth evident on day 4. In addition, the mitotic index (MI) was increased 9.6-fold at 22 hr after treatment, whereas both the [3H]thymidine ([3H]TdR) labelling index (LI) and the primer-dependent DNA polymerase labelling index (PDPI) were subnormal. Subsequent increases in both the [3H]TdR LI and PDPI, noted at 36 and 60 hr, suggested not only synchronization but also recruitment of noncycling cells. The temporal relationship between changes in the MI and the [3H]TdR LI suggested that cell cycle times (Tc's) in the perturbed tumors were similar to Tc's determined in vitro for unperturbed tumors. The DNA synthesis time was subnormal at 48 hr; however, by 84 hr after VCR administration, normal durations were reestablished. In studies designed to exploit the cell kinetic changes after VCR treatment, acute doses of 170 mg cyclophosphamide (CY)/kg administered at 60 hr after VCR resulted in variable but often dramatic tumor volume regression, while chronic CY (65 mg/kg in each injection - a total of 3 injections with 1 injection being given every 12 hr) during the interval of increased cell proliferation resulted in more uniform but less profound tumor responses. High doses of CY (300 mg/kg) at 60 hr after VCR administration resulted in greater tumor regression than that achieved with CY treatment alone.
ASJC Scopus subject areas
- Cancer Research