Schedule-dependent effect of phase-specific cytotoxic agents on production of hemolytic plaque-forming cells.
The proliferative phase of the primary response of mice to sheep red blood cells (SRBC) was used to study quantitatively the schedule-dependent effect of four phase-specific cytotoxic agents: 1-beta-D-arabinofuranosylcytosine (ARA-C), methotrexate (MTX), 5-fluorodeoxyuridine (5-FUDR), and 5-fluorouracil (5-FU). The multiple injections of ARA-C- GIVEN 24-60 HOURS AFTEr SRBC injection caused a 100-fold greater inhibition in the production of direct hemolytic plaque-forming cells (PFC) on day 4 than the maximum inhibition obtained by a single injection. A similar, but lesser, enhancing effect was observed with 5-FUDR. Although a single injection of either MTX or 5-FU given 24 or 48 hours after the immunization alone was effective in suppressing PFC production, multiple injections of MTX at 6-hour intervals could cause the same degree of inhibition with a smaller total dose. In contrast, there was no difference for 5-FU, whether given as a single injection or in a divided dose. When only two doses of cytotoxic agents were used, 8- and 14-hour intervals with ARA-C and MTX, respectively, gave the maximum degree of inhibition.
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D003561:Cytarabine / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D005467:Floxuridine / Q000008:administration & dosage; D005472:Fluorouracil / Q000008:administration & dosage; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D051379:Mice; D008806:Mice, Inbred AKR; D013997:Time Factors
D000970:Antineoplastic Agents; D005467:Floxuridine; D003561:Cytarabine; D005472:Fluorouracil; D008727:Methotrexate