Summary
Cytosine arabinoside (ara-C) was effective in altering hemolysin antibody synthesis in the rat. The kinase that activates the drug was present in adequate amounts in lymphoid tissue.
γG synthesis was completely suppressed in all experimental animals treated with 2,000 mg/kg/day for 5 days (Day 0 to Day 4 after antigen), but γG hemolysin also was absent in several animals treated with a nontoxic course of 200 mg/kg/day for 5 days and was decreased even in rats that had received 20 mg/kg/day. It was possible, with appropriate dosage schedules, selectively to inhibit γM synthesis, abbreviate its duration, or augment its synthesis and duration, as reflected in serum levels of hemolysin. No concomitant enhancement of γM and γG synthesis could be demonstrated.
Challenge of animals previously treated with ara-C resulted in secondary hemolysin responses similar to those obtained in controls. ara-C was capable of increasing as well as inhibiting humoral antibody production, the effect obtained depending upon the magnitude and scheduling of the dosage. Toxicty did not seem a sufficient explanation of the effects observed in these experiments.
Supported by Grants CA05944 and CA5138-05 from the USPHS.
Presented in part at the 58th Annual Meeting of the American Association for Cancer Research, Chicago, Illinois, April, 1967.