Department of Environmental and Occupational Health, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA, USA.
Hum Exp Toxicol. 2011 Jul;30(7):725-35. doi: 10.1177/0960327110381682. Epub 2010 Aug 20.
Epidemiological findings suggesting that formaldehyde exposure is associated with a higher risk of acute myelogenous leukemia (AML) and other hematological cancers have led to consideration of the potential mechanism of action by which inhalation of this rapidly reactive agent can cause bone marrow cancer. Two major mechanism-based arguments against formaldehyde as a leukemogen have been the difficulty in envisioning how inhaled formaldehyde might penetrate to the bone marrow; and the lack of similarity of non-cancer effects to other known human myeloleukemogens, particularly the absence of pancytopenia in humans or laboratory animals exposed to high levels. However, both of these arguments have been addressed by the recent finding of a pancytopenic effect and chromosomal abnormalities in heavily exposed Chinese workers which, if replicated, are indicative of a genotoxic effect of formaldehyde on hematopoietic stem cells that is in keeping with other known human leukemogens. Review of the body of evidence suggests an apparent discrepancy between studies in laboratory animals, which generally fail to show evidence of penetration of formaldehyde into the blood or evidence of blood or bone marrow genotoxicity, and studies of exposed humans in which there tends to be evidence of genotoxicity in circulating blood cells. One possible explanation for this discrepancy is species difference. Another possible explanation is that myeloid precursors within the nasal mucosa may be the site for leukemogenesis. However, chloromas, which are local collections of myeloid tumor cells, are rarely if ever found in the nose. Other proposed mechanisms for formaldehyde leukemogenesis are reviewed, and dose issues at the interface between the epidemiological and hematotoxicological findings are explored.
流行病学研究结果表明，甲醛暴露与急性髓性白血病（AML）和其他血液癌症的风险增加有关，这促使人们考虑吸入这种快速反应性物质会导致骨髓癌的潜在作用机制。有两个主要的基于机制的论点反对甲醛作为白血病原，即难以想象吸入的甲醛如何穿透骨髓；以及非癌症效应与其他已知的人类髓系白血病原缺乏相似性，特别是在暴露于高水平甲醛的人类或实验动物中缺乏全血细胞减少症。然而，最近发现大量暴露的中国工人出现全血细胞减少症和染色体异常，这两个论点都得到了证实，如果得到复制，这表明甲醛对造血干细胞具有遗传毒性效应，与其他已知的人类白血病原相符。对证据的回顾表明，实验室动物研究和暴露于人类的研究之间存在明显的差异，前者通常没有证据表明甲醛穿透血液或血液或骨髓的遗传毒性，而后者则倾向于表明循环血细胞中存在遗传毒性。这种差异的一个可能解释是物种差异。另一个可能的解释是，鼻黏膜内的髓样前体细胞可能是白血病发生的部位。然而，很少有或从未在鼻子中发现粒细胞肉瘤，这是局部聚集的髓样肿瘤细胞。其他甲醛致白血病的机制也进行了综述，并探讨了流行病学和血液毒性学研究结果之间的剂量问题。
