Ramsey M J, Moore D H, Briner J F, Lee D A, Olsen L a, Senft J R, Tucker J D
Biology and Biotechnology Research Program, Lawrence Livermore National Laboratory, Livermore, CA 94551-9900, USA.
Mutat Res. 1995 Oct;338(1-6):95-106. doi: 10.1016/0921-8734(95)00015-x.
Individual responses to the aging process are variable and are affected by genetic as well as environmental factors. Fluorescent in situ hybridization with whole chromosome probes ('chromosome painting') provides an efficient approach for detecting structural chromosome aberrations in human lymphocytes. This rapid and sensitive technique is an effective tool for quantifying chronic exposure to environmental agents which may result in an accumulation of cytogenetic damage with age. We have applied this technology to a normal, putatively unexposed, population to document the relationship between age and the accumulation of cytogenetic damage, as well as to establish a baseline frequency of stable aberrations. Using probes for chromosomes 1, 2 and 4 simultaneously, the equivalent of 1000 metaphases was scored for stable and unstable aberrations from each of 91 subjects ranging in age from newborns (umbilical cord bloods; n = 14) to adults aged 19 to 79 years. Each subject (or one parent of each newborn) completed an extensive questionnaire to identify possible lifestyle factors that may influence the frequency of cytogenetic damage. Our findings show a significant increase in stable aberrations (translocations and insertions) with age (p < 0.0001). We also observed age-related increases with dicentrics (p < 0.0001) and acentric fragments (p < 0.0001). Relative to the frequencies observed in cord bloods, the frequencies of stable aberrations, dicentrics, and acentric fragments in adults aged 50 and over were elevated 10.6-fold, 3.3-fold, and 2.9-fold, respectively. Nine variables other than age are significantly associated with the frequency of stable aberrations; these are: smoking (two variables), consumption of diet drinks and/or diet sweeteners (4 variables), exposure to asbestos or coal products (1 variable each), and having a previous major illness (1 variable). Newborns whose mothers smoked during pregnancy had a 1.5-fold increase in stable aberrations (p = 0.029). Repeat samples from a subset of the adults indicate that for most subjects there is little change in individual translocation frequencies over a period of two to three years. These results support the hypothesis that stable chromosome aberrations show a greater accumulation with age than do unstable aberrations and suggest that lifestyle factors contribute to the accumulation of cytogenetic damage.
个体对衰老过程的反应各不相同，且受遗传和环境因素影响。用全染色体探针进行荧光原位杂交（“染色体描绘”）为检测人类淋巴细胞中的染色体结构畸变提供了一种有效方法。这种快速且灵敏的技术是量化长期暴露于环境因素的有效工具，长期暴露可能导致细胞遗传损伤随年龄增长而积累。我们将这项技术应用于一个假定未暴露的正常人群，以记录年龄与细胞遗传损伤积累之间的关系，并确定稳定畸变的基线频率。同时使用针对1号、2号和4号染色体的探针，对91名年龄从新生儿（脐带血；n = 14）到19至79岁成年人的稳定和不稳定畸变进行了相当于1000个中期相的评分。每个受试者（或每个新生儿的一位家长）完成了一份详尽的问卷，以确定可能影响细胞遗传损伤频率的生活方式因素。我们的研究结果显示，稳定畸变（易位和插入）随年龄显著增加（p < 0.0001）。我们还观察到双着丝粒（p < 0.0001）和无着丝粒片段（p < 0.0001）随年龄增加。相对于脐带血中观察到的频率，50岁及以上成年人中稳定畸变、双着丝粒和无着丝粒片段的频率分别升高了10.6倍、3.3倍和2.9倍。除年龄外，还有九个变量与稳定畸变频率显著相关；这些变量是：吸烟（两个变量）、饮用无糖饮料和/或食用无糖甜味剂（四个变量）、接触石棉或煤炭制品（各一个变量）以及曾患重大疾病（一个变量）。母亲在孕期吸烟的新生儿稳定畸变增加了1.5倍（p = 0.029）。对一部分成年人的重复采样表明，对于大多数受试者而言，在两到三年的时间里个体易位频率变化不大。这些结果支持了这样的假设，即稳定的染色体畸变比不稳定畸变随年龄积累得更多，并表明生活方式因素会导致细胞遗传损伤的积累。
