Increased levels of chromosomal aberrations and DNA damage in a group of workers exposed to formaldehyde

Abstract

Formaldehyde (FA) is a commonly used chemical in anatomy and pathology laboratories as a tissue preservative and fixative. Because of its sensitising properties, irritating effects and cancer implication, FA accounts probably for the most important chemical-exposure hazard concerning this professional group. Evidence for genotoxic effects and carcinogenic properties in humans is insufficient and conflicting, particularly in regard to the ability of inhaled FA to induce toxicity on other cells besides first contact tissues, such as buccal and nasal cells. To evaluate the effects of exposure to FA in human peripheral blood lymphocytes, a group of 84 anatomy pathology laboratory workers exposed occupationally to FA and 87 control subjects were tested for chromosomal aberrations (CAs) and DNA damage (comet assay). The level of exposure to FA in the workplace air was evaluated. The association between genotoxicity biomarkers and polymorphic genes of xenobiotic-metabolising and DNA repair enzymes were also assessed. The estimated mean level of FA exposure was 0.38±0.03 ppm. All cytogenetic endpoints assessed by CAs test and comet assay % tail DNA (%TDNA) were significantly higher in FA-exposed workers compared with controls. Regarding the effect of susceptibility biomarkers, results suggest that polymorphisms in CYP2E1 and GSTP1 metabolic genes, as well as, XRCC1 and PARP1 polymorphic genes involved in DNA repair pathways are associated with higher genetic damage in FA-exposed subjects. Data obtained in this study show a potential health risk situation of anatomy pathology laboratory workers exposed to FA (0.38 ppm). Implementation of security and hygiene measures may be crucial to decrease risk. The obtained information may also provide new important data to be used by health care programs and by governmental agencies responsible for occupational health and safety.

Re-evaluation of the WHO (2010) formaldehyde indoor air quality guideline for cancer risk assessment

“…In previous studies, the XRCC3 allele with the same polymorphisms was investigated in the cytokinesis-block micronucleus assay with MN, nucleoplasmic bridges and nuclear buds (NBUD) as the endpoints (Ladeira et al 2013), where the Thr241Met had a higher frequency of NBUD formation. It is noted that no increase was seen in the two other endpoints or in any of the endpoints studied in the recent investigation by Costa et al (2015). In a study by Costa et al (2008), polymorphisms in ERCC1 allele rs3212986 , ERCC4 rs180067, ERCC5 rs17655 and ERCC5 rs2227869 were investigated, which are all genes involved in the NER pathway (Dhillon et al 2011); mean exposures were up to 1.58 ppm, and peak exposures up to 4.43 ppm.…”

“…However, the interpretation of the study by Aydin et al (2013) is complicated by the fact that 57 % of the workers used dust masks, suggesting a considerable and unmeasured dust concentration. It is also noted that positive comet assay tests with increased DNA migration were observed in some studies (Lin et al 2013; Costa et al 2015), which is difficult to reconcile with a direct FA effect as FA should induce DPX, causing a decrease in DNA migration (e.g. Speit et al 2009).…”

“…Dhillon et al 2011). Costa et al (2015) investigated polymorphisms of three genes, XRCC1, PARP1 and MUTYG , which participate in the BER pathway (Dhillon et al 2011), and XRCC3 , which participates in the HR pathway (de Oliveira et al 2014); mean exposures were up to 1.39 ppm and peak exposures up to 3.2 ppm. The investigated endpoints included CAs, aneuploidies, aberrant cells, multi-aberrant cells and percentage of DNA in the comet tail.…”

“…The genotoxicity of FA was investigated in blood lymphocytes of FA-exposed subjects with a CYP2E1 polymorphism (rs6413432) with the wild type carrying the T/T allele versus the combined T/A plus A/A allele group. CAs were not affected by the alleles, whereas the T/A plus A/A allele group had a lower amount of DNA in the comet tails; the authors suggested that this represented a protective effect (Costa et al 2015). …”

“…Polymorphisms of the GSTM1 , GSTT1 and GSTP1 genes have been associated with lymphohaematopoietic malignancies or predisposition to these (Dahabreh et al 2010; Bin and Luo 2013; He et al 2014). Comparing FA-induced genotoxicity in the GSTM1 null versus in the GSTM1 non-null and in the GSTT1 null versus in the GSTT1 non-null polymorphisms, respectively, showed no consistent difference between the respective null and non-null genotypes (Costa et al 2008; Jiang et al 2010; Santovito et al 2011; Zeller et al 2012; Costa et al 2015). Furthermore, FA-associated genotoxicity was investigated in the GSTP1 gene, where the isoleucine (Ile) amino acid at position 105 in the wild type (Ile/Ile) was substituted with valine (Val) with the heterozygous (Ile/Val) genotype and the mutant (Val/Val) genotype.…”