Catalán Julia, Falck Ghita C-M, Järventaus Hilkka, Kallas-Tarpila Tarja, Pitkämäki Leena, Norppa Hannu
Finnish Institute of Occupational Health, Helsinki and Lappeenranta, Finland.
Environ Mol Mutagen. 2006 Jun;47(5):345-51. doi: 10.1002/em.20213.
In the biomonitoring of human genotoxic effects, micronuclei (MN) usually are scored in phytohaemagglutinin-stimulated cultured lymphocytes. MN also can be examined in uncultured lymphocytes, which facilitates the analysis of genotoxic damage incurred in vivo. Characterization of MN in cultured lymphocytes by fluorescence in situ hybridization (FISH) has shown a clear over-representation of the X and Y chromosomes in the MN of males. However, it is not known if this phenomenon also occurs in vivo. The purpose of the present study was to assess the frequency and composition of MN formed in vivo from immunomagnetically isolated uncultured T-lymphocytes of men. To evaluate the possible effects of genotoxic exposure on in vivo MN, we examined 17 railroad workers occupationally exposed to complex chemical mixtures and 14 referents, all nonsmokers. The results showed similar total frequencies of micronucleated cells among the exposed workers and the referents. When the MN were characterized by FISH, there were no significant differences between the exposed and referents with regards to the frequency of centromere-positive or centromere-negative MN. Centromeric label was observed in 69% of all MN, indicating that most of the MN contained whole chromosomes (or chromatids). 80% of the centromere-positive MN harbored autosomes, 12% Y chromosomes, and 8% X chromosomes. The occurrence of the Y- and X-chromosomes in MN was, respectively, 5.5- and 3.8-times greater than would be expected assuming an equal contribution by all chromosomes. Thus, sex chromosomes appear to be over-represented in lymphocyte MN of men in vivo, confirming previous results obtained in vitro.
在人体遗传毒性效应的生物监测中，微核（MN）通常在植物血凝素刺激的培养淋巴细胞中进行计数。微核也可以在未培养的淋巴细胞中检测，这有助于分析体内发生的遗传毒性损伤。通过荧光原位杂交（FISH）对培养淋巴细胞中的微核进行表征，结果显示男性微核中X和Y染色体明显过度代表。然而，尚不清楚这种现象在体内是否也会发生。本研究的目的是评估从男性免疫磁珠分离的未培养T淋巴细胞中体内形成的微核的频率和组成。为了评估遗传毒性暴露对体内微核的可能影响，我们检查了17名职业性接触复杂化学混合物的铁路工人和14名对照者，他们均不吸烟。结果显示，暴露工人和对照者之间微核化细胞的总频率相似。当通过FISH对微核进行表征时，暴露组和对照组在着丝粒阳性或着丝粒阴性微核的频率方面没有显著差异。在所有微核的69%中观察到着丝粒标记，表明大多数微核包含整条染色体（或染色单体）。80%的着丝粒阳性微核含有常染色体，12%含有Y染色体，8%含有X染色体。假设所有染色体的贡献相等，微核中Y染色体和X染色体的出现频率分别比预期高5.5倍和3.8倍。因此，性染色体在男性体内淋巴细胞微核中似乎过度代表，这证实了先前在体外获得的结果。
