Further Observations on the Inhibition of Tumor Growth by Corynebacterium parvum With Cyclophosphamide. X. Effect of Treatment on Tumor Cell Kinetics in Mice2

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Abstract
With the use of female C3HeB/Fe mice, studies were done to ascertain whether the inhibition of tumor growth observed following administration of cyclophosphamide (CY) and Corynebacterlum parvum, which was greater than that resulting from the use of either agent alone, could be related to the effect of such combined chemoimmunotherapy on the cytokinetics of treated tumors. Growth characteristics and cytokinetics of untreated C3H mammary tumors were determined so that alterations resulting from therapy could be evaluated. C3H mammary tumors displayed gompertzian growth; labeling Index and growth fraction decreased, whereas cell-cycle time and DNA synthesis time Increased with tumor age and volume. A depression of the labeling index and growth fraction and an increase in DNA synthesis time occurred following a single dose of CY. The effect was maximum at approximately 5 days, with evidence of recovery by 7 days. Repeated doses of CY produced a similar cyclic effect that was less pronounced with successive doses. A single dose of C. parvum alone resulted in changes similar to those observed with CY. However, they occurred more, promptly (maximum at 1 day) and were of lesser magnitude and shorter duration. The use of C. parvum and CY therapy prolonged the kinetic changes caused by CY. The effect of the chemoimmunotherapy Interval was evaluated, and a chemoimmunotherapy interval of +4 days produced greater kinetic alterations than did a chemoimmunotherapy interval of −3 or zero days. That interval (+4 days) has been most effective in inhibiting tumor growth. Multiple courses of combination therapy resulted in a reduction in labeling index and growth fraction and an increase in DNA synthesis time greater than those produced by CY alone. These results were in keeping with findings relative to tumor growth. The findings indicate that the immunopotentlator C. parvum affects tumor cell kinetics and that the greater inhibition of tumor growth resulting after chemoimmunotherapy is reflected in the cytokinetic changes occurring during such treatment.

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