Academic journal article Environmental Health Perspectives

Formaldehyde and Epigenetic Alterations: microRNA Changes in the Nasal Epithelium of Nonhuman Primates

Academic journal article Environmental Health Perspectives

Formaldehyde and Epigenetic Alterations: microRNA Changes in the Nasal Epithelium of Nonhuman Primates

Article excerpt

BACKGROUND: Formaldehyde is an air pollutant present in both indoor and outdoor atmospheres. Because of its ubiquitous nature, it is imperative to understand the mechanisms underlying formaldehyde-induced toxicity and carcinogenicity. MicroRNAs (miRNAs) can influence disease caused by environmental exposures, yet miRNAs are understudied in relation to formaldehyde. Our previous investigation demonstrated that formaldehyde exposure in human lung cells caused disruptions in miRNA expression profiles in vitro.

OBJECTIVES: Using an in vivo model, we set out to test the hypothesis that formaldehyde inhalation exposure significantly alters miRNA expression profiles within the nasal epithelium of nonhuman primates.

METHODS: Cynomolgus macaques were exposed by inhalation to approximately 0, 2, or 6 ppm formaldehyde for 6 hr/day for 2 consecutive days. Small RNAs were extracted from nasal samples and assessed for genome-wide miRNA expression levels. Transcriptional targets of formaldehyde-altered miRNAs were computationally predicted, analyzed at the systems level, and assessed using real-time reverse transcriptase polymerase chain reaction (RT-PCR).

RESULTS: Expression analysis revealed that 3 and 13 miRNAs were dysregulated in response to 2 and 6 ppm formaldehyde, respectively. Transcriptional targets of the miRNA with the greatest increase (miR-125b) and decrease (miR-142-3p) in expression were predicted and analyzed at the systems level. Enrichment was identified for miR-125b targeting genes involved in apoptosis signaling. The apoptosis-related targets were functionally tested using RT-PCR, where all targets showed decreased expression in formaldehyde-exposed samples.

CONCLUSIONS: Formaldehyde exposure significantly disrupts miRNA expression profiles within the nasal epithelium, and these alterations likely influence apoptosis signaling.

KEY WORDS: apoptosis, epigenetics, formaldehyde, microRNA, primate, systems biology. Environ Health Perspect 121:339-344 (2013). http://dx.doi.org/10.1289/ehp.1205582 [Online 15 January 2013]

Formaldehyde is a ubiquitous chemical that has been the focus of many toxicological and epidemiological investigations. Epidemiological studies have found that formaldehyde is associated with increased risk of childhood asthma (McGwin et al. 2010), acute respiratory tract illness (Tuthill 1984), sinonasal cancer (Luce et al. 1993), nasopharyngeal cancer (Vaughan et al. 2000), and possibly leukemia (Beane Freeman et al. 2009). In toxicological studies, formaldehyde has been shown to cause nasal squamous cell carcinomas in rats (Kerns et al. 1983; Monticello et al. 1996) and, to a lesser extent, in mice (Kerns et al. 1983). Formaldehyde is currently classified as a known human carcinogen by the International Agency for Research on Cancer (IARC 2006).

Formaldehyde is present in both indoor and outdoor atmospheres. In indoor environments, sources of formaldehyde include plywood, furniture, particle board, certain insulation materials, carpets, paints and varnishes, textiles, tobacco smoke, and the use of formaldehyde as a disinfectant [IARC 2006; National Toxicology Program (NTP) 2011]. In outdoor environments, formaldehyde is produced as both a primary and secondary air pollutant via atmospheric photochemistry (IARC 2006; NTP 2011). Some of the highest formaldehyde exposures occur in occupational settings such as industries involving resin, plastics, wood, paper, insulation, textiles, chemical productions, disinfectants, and embalming products (IARC 2006; NTP 2011). Formaldehyde is also formed in vivo through the metabolism and processing of drugs, dietary agents, and amino acids (O'Brien et al. 2005). Because of the constant presence of both endogenous and environmental formaldehyde exposure, coupled with its deleterious health effects, understanding the exposure response and biological basis of formaldehyde-induced health effects is of utmost importance. …

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