Tucker J D, Lee D A, Ramsey M J, Briner J, Olsen L, Moore D H
Biology and Biotechnology Research Program, L-452 Lawrence Livermore National Laboratory, Livermore, CA 94551.
Mutat Res. 1994 Oct-Dec;313(2-3):193-202. doi: 10.1016/0165-1161(94)90049-3.
Chromosome painting has been shown to be a valid and rapid method for quantifying structural chromosome rearrangements in human lymphocytes. The method is particularly useful for detecting stable aberrations which are difficult and expensive to quantify with classical methods. The inherent stability of translocations has enabled them to be used as a biodosimeter for chronic and temporally displaced exposure to radiation. Translocations may also be useful for quantifying chronic exposure to other environmental agents which may result in an accumulation of cytogenetic damage with age. Most exposures are chronic and occur at low rates, and conventional cytogenetic methods such as dicentric analysis are not expected to be informative. To understand the extent to which age and lifestyle factors impact the frequency of stable aberrations, we have performed chromosome painting on metaphase-arrested lymphocytes cultured from 47 healthy adults ranging in age from 19 to 77 years, and from umbilical cord blood obtained from eight healthy full-term infants. All subjects had previously been screened to eliminate those who had received significant occupational or accidental exposure to radiation or chemicals, and none had received chemo- or radiotherapy. Due to the infrequent occurrence of stable aberrations in peripheral lymphocytes, we analyzed the equivalent of more than 1100 metaphase cells from each of these 55 people. An average of one cell in 130 (0.77%) was observed to have a translocation or a stable insertion. A significant relationship between stable aberrations and the square of the age is apparent (R2 = 0.69, Y = 0.0615 + 0.000304 age2; p < 0.00001). These results support the hypothesis that stable aberrations accumulate with time, and are likely to integrate adverse environmental exposure.
染色体描绘已被证明是一种有效且快速的方法，可用于量化人类淋巴细胞中的染色体结构重排。该方法对于检测稳定的畸变特别有用，而用传统方法对这些畸变进行量化既困难又昂贵。易位的固有稳定性使其能够用作生物剂量计，用于评估长期和有时间间隔的辐射暴露。易位也可能有助于量化长期暴露于其他环境因素的情况，这些因素可能导致随着年龄增长细胞遗传损伤的积累。大多数暴露是长期的，且发生率较低，传统的细胞遗传学方法如双着丝粒分析预计不会提供有用信息。为了了解年龄和生活方式因素对稳定畸变频率的影响程度，我们对47名年龄在19至77岁之间的健康成年人以及8名健康足月婴儿的脐带血培养的中期停滞淋巴细胞进行了染色体描绘。所有受试者之前都经过筛选，以排除那些曾接受过大量职业或意外辐射或化学物质暴露的人，且没有人接受过化疗或放疗。由于外周淋巴细胞中稳定畸变的发生率较低，我们对这55人中的每一个人分析了超过1100个中期细胞。平均每130个细胞中有1个（0.77%）被观察到有易位或稳定插入。稳定畸变与年龄的平方之间存在显著关系（R2 = 0.69，Y = 0.0615 + 0.000304年龄²；p < 0.00001）。这些结果支持了稳定畸变随时间积累的假设，并且可能整合了不利的环境暴露。
