临床时讯 ＞ 临床研究
英国莱斯特大学的研究人员在美国《国家科学院院刊》（Proceedings of the National Academy of Sciences）上报告说，他们测试了3种常用来治疗癌症的化疗药物，它们是环磷酰胺、丝裂霉素C和甲基苄肼。研究人员给实验鼠服用相当于临床治疗剂量的药物，结果发现，虽然实验鼠是在停药数月后才繁殖，但它们后代的基因组中还是出现了异常变异。
研究人员尤里·杜布罗瓦（Yuri E. Dubrova）说，这是一个引人关注的现象，至于这些药物在人类患者体内会不会有类似作用，还不能简单类推。这是因为实验鼠的寿命只有约两年，比人类要短得多，它们服药与繁殖后代之间的时间间隔不是很长，而人类可选择长期停药后再生育。
Proc Natl Acad Sci U S A. 2012 Jan 30. [Epub ahead of print]
Exposure to anticancer drugs can result in transgenerational genomic instability in mice.
Glen CD, Dubrova YE.
Department of Genetics, University of Leicester, Leicester LE1 7RH, United Kingdom.
The genetic effects of human exposure to anticancer drugs remain poorly understood. To establish whether exposure to anticancer drugs can result not only in mutation induction in the germ line of treated animals, but also in altered mutation rates in their offspring, we evaluated mutation rates in the offspring of male mice treated with three commonly used chemotherapeutic agents: cyclophosphamide, mitomycin C, and procarbazine. The doses of paternal exposure were approximately equivalent to those used clinically. Using single-molecule PCR, the frequency of mutation at the mouse expanded simple tandem repeat locus Ms6-hm was established in DNA samples extracted from sperm and bone marrow of the offspring of treated males. After paternal exposure to any one of these three drugs, expanded simple tandem repeat mutation frequencies were significantly elevated in the germ line (sperm) and bone marrow of their offspring. This observed transgenerational instability was attributed to elevated mutation rates at the alleles derived from both the exposed fathers and from the nonexposed mothers, thus implying a genome-wide destabilization. Our results suggest that paternal exposure to a wide variety of mutagens can result in transgenerational instability manifesting in their offspring. Our data also raise important issues concerning delayed transgenerational effects in the children of survivors of anticancer therapy.