Cell Kinetics After Vincristine Treatment of C3H/He Spontaneous Mammary Tumors: I mplications for Therapy2

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Abstract
Cell kinetics in spontaneous mammary tumors in inbred C3H/HeJ mice was studied by 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 hours after treatment, whereas both the [3H]thymidine ([3H]TdR) labeling index (LI) and the primer-dependent DNA polymerase labeling Index (POPI) were subnormal. Subsequent increases in both the [3H]TdR LI and POPI, noted at 36 and 60 hours, 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 hours; however, by 84 hours 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 (CV)/kg administered at 60 hours after VCR resulted in variable but often dramatic tumor volume regression, while chronic CV (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 CV (300 mg/kg) at 60 hours after VCR administration resulted in greater tumor regression than that achieved with CV treatment alone.