RESUMO
The combined effects of mitomycin C (MMC) and thio-tepa (TT) with gamma-ray doses of 5 and 9 Gy on mouse stem cells were studied using the spermatocyte test. Both chemicals induced very low yields of translocations after single treatments. In combined treatments with a dose of 5 Gy, a subadditive effect of MMC and an additive effect of TT were found. Combined with a dose of 9 Gy the compounds potentiated the effect of radiations. Up to now, most of the chemicals tested have shown additive effects when combined with doses of the ascending part of the dose-response curve and potentiating effects when combined with doses of its descending part. This has been considered additional confirmation of the concept that depletion of any kind of spermatogonia is sufficient to modify the genetic response of stem cells. However, the subadditive and additive responses found could be considered evidence that common biological mechanisms can modulate the response to combined treatments of chemicals and ionizing radiations.
Assuntos
Raios gama , Mitomicinas/toxicidade , Radiação Ionizante , Espermatogônias , Espermatozoides , Tiotepa/toxicidade , Translocação Genética , Animais , Relação Dose-Resposta a Droga , Relação Dose-Resposta à Radiação , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Mitomicina , Espermatogônias/efeitos dos fármacos , Espermatogônias/efeitos da radiação , Espermatozoides/efeitos dos fármacos , Espermatozoides/efeitos da radiação , Translocação Genética/efeitos dos fármacos , Translocação Genética/efeitos da radiaçãoRESUMO
Using 3-way differential staining (TWD) of sister chromatids, the fate of DNA lesions involved in sister-chromatid exchange (SCE) formation was determined in murine bone marrow cells in vivo, after treatment with either mitomycin C (MMC) or cyclophosphamide (CP). Both MMC (2.6 mg/kg b.w.) and CP (7 mg/kg b.w.) induced an SCE frequency near the expected in the 2 subsequent cell divisions, but the frequency of SCE occurring at the same locus in successive cell divisions was substantially lower than expected. The results are compared with previous data obtained after exposure to gamma-rays. A model of SCE induction is proposed.