Analysis of Leukemia-Specific Aneuploidies in Cultured Myeloid Progenitor Cells in the Absence and Presence of Formaldehyde Exposure

• Published in: Toxicological sciences Vol. 128; no. 1; pp. 72 - 78
• Main Authors: Kuehner, Stefanie, Schlaier, Martina, Schwarz, Klaus, Speit, Günter
• Format: Journal Article
• Language: English
• Published: United States 01.07.2012
• Subjects: Aneuploidy; Cells, Cultured; Formaldehyde - toxicity; Humans; In Situ Hybridization, Fluorescence; Leukemia - genetics; Leukemia - pathology; Myeloid Progenitor Cells - cytology; Myeloid Progenitor Cells - drug effects
• ISSN: 1096-6080; 1096-0929; 1096-0929
• DOI: 10.1093/toxsci/kfs126

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.