The response of murine stem spermatogonia to radiation combined with 3-aminobenzamide.
The influence of 3-aminobenzamide (3-AB) on the radiation response of the stem spermatogonia of the CBA mouse has been investigated. Doses of 3-AB from 66 to 450 mg/kg, administered 1 h before irradiation, significantly enhanced stem-cell killing. Enhancement was observed when 3-AB (450 mg/kg) was given up to 5 h before, but not if administered after, irradiation. When radiation was delivered at a lower dose rate (5 cGy/min compared to 180 cGy/min) significant dose sparing was achieved for radiation alone. Pretreatment with 3-AB resulted in slightly less enhancement at the low dose rate than at the high. Split-dose studies (9 Gy total dose) with radiation alone resulted in a recovery ratio of 1.4-1.5. Administration of 3-AB before the first dose resulted in a similar recovery ratio, but if given immediately after the first dose the ratio was smaller. Pretreatment of mice with the radiosensitizer RSU-1069 indicated that at least some of the stem cells were radiobiologically hypoxic. We suggest therefore that the enhancement of spermatogonial stem-cell killing by 3-AB is not entirely due to inhibition of repair processes but may also involve modification of the oxygen status of the testis.
D000818:Animals; D001549:Benzamides / Q000494:pharmacology*; D003114:Colony-Forming Units Assay; D004260:DNA Repair / Q000187:drug effects; D005720:Gamma Rays; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D008920:Misonidazole / Q000031:analogs & derivatives / Q000494:pharmacology; D010100:Oxygen / Q000378:metabolism; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011836:Radiation Tolerance / Q000187:drug effects; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology; D013091:Spermatogenesis / Q000187:drug effects / Q000528:radiation effects; D013093:Spermatogonia / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects*; D013094:Spermatozoa / Q000528:radiation effects*; D013234:Stem Cells / Q000187:drug effects / Q000528:radiation effects
D001549:Benzamides; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011838:Radiation-Sensitizing Agents; C041712:1-(2-nitro-1-imidazolyl)-3-aziridino-2-propanol; D008920:Misonidazole; C025160:3-aminobenzamide; D010100:Oxygen