Zhang Luoping, Lan Qing, Guo Weihong, Li Guilan, Yang Wei, Hubbard Alan E, Vermeulen Roel, Rappaport Stephen M, Yin Songnian, Rothman Nathaniel, Smith Martyn T
School of Public Health, 140 Warren Hall, University of California, Berkeley, CA 94720-7360, USA.
Chem Biol Interact. 2005 May 30;153-154:117-22. doi: 10.1016/j.cbi.2005.03.016. Epub 2005 Apr 19.
Benzene is an established human leukemogen. The mechanism of benzene-induced leukemogenesis, however, remains unclear, but chromosomal damage is thought to play a critical role. We previously reported that the loss of chromosomes 5 and 7 (monosomy 5 and 7) and the gain of chromosomes 8 and 21 (trisomy 8 and 21) are significantly increased in benzene-exposed workers in comparison to matched controls. To determine if selective effects of benzene can occur, we employed three-color painting on an 8-square slide to screen numerical changes in all 24 human chromosomes (OctoChrome FISH) in a pilot study of 11 subjects (6 exposed to >5 ppm benzene and 5 age- and sex-matched controls). The effects of benzene on each chromosome were assessed as the incidence rate ratio (IRR) from a Poisson regression model with the strongest effects being reflected by the highest IRR values. Monosomy of chromosomes 5, 6, 7 and 10 had the highest IRRs and statistical significance in this preliminary study (IRR>2.5, p<0.01). On the other hand, the monosomy levels of six other chromosomes (1, 4, 9, 11, 22 and Y) were unchanged in the exposed workers with IRRs close to 1.0. Similarly, selective effects were also observed on trisomy induction with chromosomes 8, 9, 17, 21 and 22 (IRR>2.5, p<0.01). These results suggest that benzene has the capability of producing selective effects on certain chromosomes, which is supported by our in vitro findings showing that chromosomes 5 and 7 are more sensitive to loss than other chromosomes following exposure to benzene metabolites. We are currently investigating potential mechanisms for this induction of selective aneuploidy.
苯是一种已确定的人类白血病致癌物。然而，苯诱导白血病发生的机制仍不清楚，但染色体损伤被认为起着关键作用。我们之前报道过，与匹配的对照组相比，接触苯的工人中5号和7号染色体缺失（5号和7号染色体单体性）以及8号和21号染色体增加（8号和21号染色体三体性）的情况显著增多。为了确定苯是否会产生选择性影响，我们在一项针对11名受试者（6名接触苯浓度>5 ppm，5名年龄和性别匹配的对照组）的初步研究中，使用八色玻片上的三色染色体描绘技术来筛查所有24条人类染色体的数目变化（OctoChrome荧光原位杂交技术）。苯对每条染色体的影响通过泊松回归模型的发病率比（IRR）进行评估，最强的影响由最高的IRR值反映。在这项初步研究中，5号、6号、7号和10号染色体单体性的IRR最高且具有统计学意义（IRR>2.5，p<0.01）。另一方面，其他六条染色体（1号、4号、9号、11号、22号和Y染色体）的单体性水平在接触苯的工人中没有变化，IRR接近1.0。同样，在三体性诱导方面也观察到了选择性影响，涉及8号、9号、17号、21号和22号染色体（IRR>2.5，p<0.01）。这些结果表明，苯能够对某些染色体产生选择性影响，我们的体外研究结果也支持这一点，即接触苯代谢物后，5号和7号染色体比其他染色体更容易发生缺失。我们目前正在研究这种选择性非整倍体诱导的潜在机制。
