Influence of timing of cytotoxic drug treatment on the response of murine clonogenic spermatogonia to X-irradiation.
The enhancement of radiation-induced stem spermatogonial cell killing by three cytotoxic compounds has been investigated using an in vivo clonogenic assay. Drug doses (carmustine (BCNU), 15 mg/kg; cyclophosphamide (CY), 150 mg/kg; procarbazine (PCB), 200 mg/kg) were chosen to kill a high proportion of differentiated spermatogonia but few stem-cells, as assessed by sperm-head counts (SHC) at 29 and 56 days respectively. Drug doses were administered up to 14 days prior to or after local irradiation with 9 Gy of 230 kVp X-rays. BCNU produced a moderate enhancement of damage that was relatively independent of time. Both CY and PCB produced a considerable enhancement of damage especially when administered 1 to 3 days before irradiation. Enhancement in the case of PCB consisted largely of a vertical displacement of the radiation dose-response curves, but with additional evidence for possible changes in slope.
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002330:Carmustine / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D003520:Cyclophosphamide / Q000494:pharmacology; D004307:Dose-Response Relationship, Radiation; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D011344:Procarbazine / Q000494:pharmacology; D013093:Spermatogonia / Q000187:drug effects / Q000528:radiation effects*; D013094:Spermatozoa / Q000528:radiation effects*; D013997:Time Factors
D000970:Antineoplastic Agents; D011344:Procarbazine; D003520:Cyclophosphamide; D002330:Carmustine