Zhang L, Wang Y, Shang N, Smith M T
Division of Environmental Health Sciences, School of Public Health, University of California, Berkeley 94720-7360, USA.
Leuk Res. 1998 Feb;22(2):105-13. doi: 10.1016/s0145-2126(97)00157-4.
Two of the most common cytogenetic changes in therapy- and chemically-related leukemia are the loss and long (q) arm deletions of chromosomes 5 and 7 (i.e. -5, -7, del(5q) and del(7q)). We have used a novel fluorescence in situ hybridization (FISH) procedure to determine if the benzene metabolites hydroquinone (HQ) and 1,2,4-benzenetriol (BT) can induce these specific changes in human lymphocytes cultured as whole blood. Metaphase spreads were prepared and hybridized with centromeric probes for chromosomes 1, 5 and 7 and sequence specific probes for 5q31 and 7q36-qter. HQ and BT significantly increased monosomy 5 and 7 by 3-5 fold (p < 0.0001). Both HQ and BT also significantly increased the rate of del(5q) and del(7q) by 8-12 fold (p < 0.0001). Chromosome 7 was especially susceptible to aneusomy induction by HQ and BT at low doses. These results show that metabolites of benzene are highly effective in inducing changes in chromosomes 5 and 7 that are involved in the development of myeloid leukemia.
治疗相关和化学相关白血病中两种最常见的细胞遗传学改变是5号和7号染色体的缺失以及长臂(q)缺失(即-5、-7、del(5q)和del(7q))。我们使用了一种新型荧光原位杂交(FISH)方法来确定苯代谢产物对苯二酚(HQ)和1,2,4-苯三酚(BT)是否能在作为全血培养的人类淋巴细胞中诱导这些特定改变。制备中期染色体铺片,并与1号、5号和7号染色体的着丝粒探针以及5q31和7q36-qter的序列特异性探针杂交。HQ和BT使5号和7号染色体单体显著增加3至5倍(p < 0.0001)。HQ和BT还使del(5q)和del(7q)的发生率显著增加8至12倍(p < 0.0001)。7号染色体在低剂量时对HQ和BT诱导的非整倍体尤其敏感。这些结果表明,苯代谢产物在诱导与髓系白血病发生相关的5号和7号染色体改变方面非常有效。