多年来，有关涉及辐射的癌症疗法对幸存者后代的影响进行了很多的研究。这是因为辐射已知能够导致细胞内的突变。而有关癌症治疗中的化疗药物的代际效应还没有很好的研究。现在，英国莱斯特大学的Colin Glen和Yuri Dubrova领导的研究表明，以接受化疗药物的雄性大鼠为父系的幼崽中比它们的父亲有多至2倍的突变。研究结果发表于PNAS上。
在过去的10年中，首席研究员、遗传学家Dubrova一直在研究癌症疗法对动物的影响，大多数集中于放射治疗的后遗症。然而最近，他开始调查化疗药物对后代甚至后面数代可能的遗传学影响。这类药物是系统性全身性给药，不接受放射治疗的其他身体部分也被包含在内，这可能使化疗的结果更糟。为了找到答案，他和他的同事将3种最常见的化疗药物在雄性小鼠上进行了研究，根据小鼠的大小给予相对的剂量。随后将这些雄性小鼠和未接受治疗的雌性小鼠进行交配，对产生的雄性后代的部分基因组进行了研究，结果发现了比父母任一方多至2倍的突变。
作者认为，公众不应对他们的研究结果产生恐慌，因为大多数癌症患者年龄都太大而无法受孕，或由于接受治疗而不育，使得接受治疗的儿童成为可能存在风险的一组人。但他们说，他们的结果还需要在适当的范围内开展。研究中使用的小鼠只生存了几年，在接受化学物质之后很快产生了后代，而那些接受化疗药物的儿童要达到生育年龄还需要很长的时间。要查明时间的滞后是否能够在生育之前对受损的基因进行修复，则需要用寿命更长的动物进行研究。
研究的另一个有趣发现是，后代中遗传自未接受任何药物的母亲的DNA，受到了与来自接受药物的父亲同样方式的影响，这种情况在以前的其他研究中也存在，但现在依然不清楚原因。（生物谷bioon.com）
doi:10.1073/pnas.1119396109
PMC:
PMID:
Exposure to anticancer drugs can result in transgenerational genomic instability in mice
Colin D. Glen and Yuri E. Dubrova
Abstract：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.
