Institut für Humangenetik, Universität Ulm, D-89081 Ulm, Germany.
Toxicol Sci. 2012 Jul;128(1):72-8. doi: 10.1093/toxsci/kfs126. Epub 2012 Apr 3.
A recently published human study suggested that exposure to formaldehyde (FA) at the workplace might induce leukemia-specific aneuploidies (monosomy 7 and trisomy 8) in cultured myeloid progenitor cells. Despite its preliminary character, this study was considered by the International Agency for Research on Cancer to be a potential mechanistic explanation for the induction of leukemia by FA. To further evaluate the reliability of these findings, chromosome preparations from cultured myeloid progenitor cells (obtained from blood samples of five healthy subjects) were analyzed by fluorescence in situ hybridization (FISH) for spontaneously occurring numerical aberrations after cultivation for 9 days. FISH analysis with probes for chromosomes 6, 7, and 8 revealed that the baseline frequency of aneuploid metaphases is similar and rather low for all three chromosomes tested. More monosomies than trisomies were measured. We also exposed myeloid progenitor cells during the whole cultivation period to FA and determined the frequency of aneuploidies after 9 days of cultivation. The results clearly indicate that FA did not induce aneuploidy under these experimental conditions. In contrast, aneuploidy was induced under these conditions by the known aneugen vincristine. Myeloid progenitor cells from healthy subjects were not particularly sensitive toward the cytotoxic action of FA. Colony forming ability in the presence of FA was not reduced to a higher degree than in cultured cell lines (A549; V79). Our results do not support the assumption of a specific effect of FA on myeloid progenitor cells as a potential mechanism for the induction of leukemia.
最近发表的一项人类研究表明，工作场所接触甲醛（FA）可能会导致培养的髓系祖细胞中出现白血病特异性非整倍体（单体 7 和三体 8）。尽管该研究具有初步特征，但国际癌症研究机构认为，这是 FA 诱导白血病的潜在机制解释。为了进一步评估这些发现的可靠性，通过荧光原位杂交（FISH）分析培养的髓系祖细胞（取自 5 名健康受试者的血液样本）中的染色体，以检测培养 9 天后自发发生的数量异常。用针对染色体 6、7 和 8 的探针进行 FISH 分析表明，所有三个测试的染色体的非整倍体中期的基线频率相似且相当低。测量到的单体数多于三体数。我们还在整个培养期间使髓系祖细胞接触 FA，并在培养 9 天后确定非整倍体的频率。结果清楚地表明，在这些实验条件下，FA 不会诱导非整倍性。相比之下，在这些条件下，已知的致整倍体长春新碱诱导了非整倍体。来自健康受试者的髓系祖细胞对 FA 的细胞毒性作用并不特别敏感。FA 存在下的集落形成能力并未比培养细胞系（A549；V79）降低更高程度。我们的结果不支持 FA 对髓系祖细胞具有特定作用的假设，作为诱导白血病的潜在机制。
