Meistrich M L, van Beek M E, Liang J C, Johnson S L, Lu J
Department of Experimental Radiotherapy, University of Texas M.D. Anderson Cancer Center, Houston 77030.
Cancer Res. 1990 Jan 15;50(2):370-4.
The mutagenic effects of doxorubicin (Adriamycin, ADR) on mouse spermatogonial stem cells were examined by analysis of spermatocyte chromosomes and of dominant lethality transmitted through the spermatozoa. The effects of ADR on mutations, cytotoxicity, and sperm head abnormalities were compared with those of radiation. The cytotoxic effect of 6 Gy of gamma-radiation on stem spermatogonia was equivalent to about 4-5 mg ADR/kg. Chromosomal translocations were observed in 0.6% of the spermatocytes of mice treated with ADR (2-6 mg/kg). In contrast, 6 Gy of radiation induced translocations in 11.1% of spermatocytes. No increase in dominant lethality was observed after treatment with ADR at doses up to 6 mg/kg, while the frequency after 6 Gy of radiation was 3.6%. Based on these results, ADR would be expected to be only a weak inducer of balanced chromosomal rearrangements. Because ADR at 4.5 mg/kg was much weaker than 6 Gy of gamma-radiation at inducing chromosomal translocations, but just as effective at inducing sperm head abnormalities, the level of sperm head abnormalities is not indicative of balanced chromosomal rearrangements induced in stem spermatogonia by cytotoxic agents.
通过分析精母细胞染色体以及经精子传递的显性致死率，研究了阿霉素（阿霉素，ADR）对小鼠精原干细胞的诱变作用。将阿霉素对突变、细胞毒性和精子头部异常的影响与辐射的影响进行了比较。6 Gy的γ射线对精原干细胞的细胞毒性作用相当于约4-5 mg阿霉素/千克。在用阿霉素（2-6 mg/千克）处理的小鼠的0.6%的精母细胞中观察到染色体易位。相比之下，6 Gy的辐射在11.1%的精母细胞中诱导了易位。在高达6 mg/千克的剂量下用阿霉素处理后未观察到显性致死率增加，而6 Gy辐射后的频率为3.6%。基于这些结果，预计阿霉素只是平衡染色体重排的弱诱导剂。由于4.5 mg/千克的阿霉素在诱导染色体易位方面比6 Gy的γ射线弱得多，但在诱导精子头部异常方面同样有效，因此精子头部异常的水平并不能表明细胞毒性剂在精原干细胞中诱导的平衡染色体重排情况。
