Occupational Exposure to Formaldehyde, Hematotoxicity, and Leukemia-Specific Chromosome Changes in Cultured Myeloid Progenitor Cells

Abstract

There are concerns about the health effects of formaldehyde exposure, including carcinogenicity, in light of elevated indoor air levels in new homes and occupational exposures experienced by workers in health care, embalming, manufacturing, and other industries. Epidemiologic studies suggest that formaldehyde exposure is associated with an increased risk of leukemia. However, the biological plausibility of these findings has been questioned because limited information is available on the ability of formaldehyde to disrupt hematopoietic function. Our objective was to determine if formaldehyde exposure disrupts hematopoietic function and produces leukemia-related chromosome changes in exposed humans. We examined the ability of formaldehyde to disrupt hematopoiesis in a study of 94 workers in China (43 exposed to formaldehyde and 51 frequency-matched controls) by measuring complete blood counts and peripheral stem/progenitor cell colony formation. Further, myeloid progenitor cells, the target for leukemogenesis, were cultured from the workers to quantify the level of leukemia-specific chromosome changes, including monosomy 7 and trisomy 8, in metaphase spreads of these cells. Among exposed workers, peripheral blood cell counts were significantly lowered in a manner consistent with toxic effects on the bone marrow and leukemia-specific chromosome changes were significantly elevated in myeloid blood progenitor cells. These findings suggest that formaldehyde exposure can have an adverse effect on the hematopoietic system and that leukemia induction by formaldehyde is biologically plausible, which heightens concerns about its leukemogenic potential from occupational and environmental exposures.

Genotoxic effects in occupational exposure to formaldehyde: A study in anatomy and pathology laboratories and formaldehyde-resins production

“…Our results in blood lymphocytes can be an indication that cytogenetic effects can be found in tissues distant from the area of initial contact (nasopharyngeal) and even reach the bone marrow and cause toxicity, supporting the thesis of Zhang and colleagues [1,29]. A significant positive correlation between MN frequency (both in peripheral blood lymphocytes and in epithelial buccal cells) and the duration of FA exposure (years of employment) was found (Table 4).…”

“…The only two studies concerning the association between exposure to FA and nasopharyngeal cancer that presented data on exposure to ceiling concentrations obtained higher relative risk values compared with the other studies [1,12,26]. Moreover, other groups also suggested ceiling concentrations as the most important exposure metric, when attempting to define the relative risk of myeloid leukaemia in workers exposed to FA [1,[27][28][29].…”

“…Also, there is no credible experimental animal model for FAinduced leukaemia [40,41]. However, Zhang et al hypothesize that FA may act on bone marrow directly or, alternatively, may cause leukaemia by damaging the hematopoietic stem or early progenitor cells that are located in the circulating blood or nasal passages, which would then travel to bone marrow and become leukemic stem cells [1,29]. Nevertheless, our findings are consistent with other previous studies on epithelial cells and also on peripheral lymphocytes [42][43][44].…”

Genotoxicity Biomarkers: Application in Histopathology Laboratories

“…The International Agency for Research on Cancer (IARC) reclassified FA as a human carcinogen (group 1) in June 2004 based on "sufficient epidemiological evidence that FA causes nasopharyngeal cancer in humans" (IARC, 2006;Zhang et al, 2009). In their review, IARC also concluded that there was ''strong but not sufficient evidence for a causal association between leukaemia and occupational exposure to FA'' (Zhang et al, 2009(Zhang et al, , 2010. However, some studies have also led to mixed results and inconclusive evidence (Franks, 2005;Speit et al, 2010).…”

Response letter to the Editor RE: Formaldehyde and leukemia: missing evidence!

“…He notes the omission of a letter exchange [3] concerning evidence for hematotoxicity and chromosome damage among Chinese workers exposed to formaldehyde [4]. Although this exchange raised some provocative questions, it does not alter our conclusion that the proposed leukemogenesis mechanisms for formaldehyde remain unsubstantiated.…”