Skip to main content

Advertisement

Log in

Gene expression profiling in lung tissues from rats exposed to formaldehyde

  • Organ Toxicity and Mechanisms
  • Published:
Archives of Toxicology Aims and scope Submit manuscript

Abstract

Formaldehyde is a ubiquitous toxic organic compound recently classified as a carcinogen by the International Agency for Research on Cancer and one of the major factors causing sick building syndrome. In this study, we have investigated the effects of formaldehyde on mRNA expression in rat lung tissues by applying genomics. Rats were exposed to ambient air and two different concentrations of formaldehyde (0, 5, 10 ppm) for 2 weeks at 6 h/day and 5 days/week in an inhalation chamber. Malondialdehyde (MDA) assay and carbonyl spectrometric assay were conducted to determine lipid peroxidation and protein oxidation levels and Comet assays were used for genotoxicity evaluation. Level of MDA, carbonyl insertion and DNA damage in the lungs of rats exposed to FA were found to be dose dependently increased. Gene expression was evaluated by using a bio-array hybridization analysis. A total of 21 (2 up- and 19 down-regulated) genes were identified as biomarkers for formaldehyde effects. Several differentiated gene groups were found. Genes involved in apoptosis, immunity, metabolism, signal transduction, transportation, coagulation and oncogenesis were found to be up- and down-regulated. Among these genes, the mRNA expressions of cytochrome P450, hydroxymethylbilane synthase, glutathione reductase, carbonic anhydrase 2, natriuretic peptide receptor 3, lysosomal associated protein transmembrane 5, regulator of G-protein signaling 3, olfactomedin related ER localized protein, and poly (ADP-ribose) polymerase-1 were confirmed by quantitative RT-PCR analysis. In summary, the MDA lipid peroxidation and the carbonyl protein oxidation assays showed that cytotoxic effects increased with increasing formaldehyde levels. Genomic analysis showed that 21 genes were up- or down-regulated. Of these genes, nine were confirmed by quantitative RT-PCR and could be potential biomarkers for human diseases associated with formaldehyde exposure.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  • Adibhatla RM, Hatcher JF (2006) Phospholipase A2, reactive oxygen species, and lipid peroxidation in cerebral ischemia. Free Rad Biol Med 40:376–387

    Article  CAS  Google Scholar 

  • Adibhatla RM, Hatcher JF, Dempsey RJ (2006) Forum original research communication; phospholipase A2, hydroxyl radical, and lipid peroxidation in transient cerebral ischemia. Antioxid Redox Signal 5:647–654

    Article  CAS  Google Scholar 

  • Agarwal R, Chase SD (2002) Rapid fluorimetric-liquid chromatographic determination of malondialdehyde in biological samples. J Chromatogr B Analyt Technol Biomed Life Sci 775:121–126

    Article  PubMed  CAS  Google Scholar 

  • Cheng G, Shi Y, Sturla SJ, Jalas JR, McIntee EJ, Villalta PW, Wang M, Hecht SS (2003) Reactions of formaldehyde plus acetaldehyde with deoxyguanosine and DNA: formation of cyclic deoxyguanosine adducts and formaldehyde cross-links. Chem Res Toxicol 16:145–152

    Article  PubMed  CAS  Google Scholar 

  • Corvi R (2002) Genomics: an in vitro toxicology point of view. Altern Lab Anim 2:129–131

    Google Scholar 

  • Cosma GN, Marchok AC (1988) Benzo[a]pyrene-and formaldehyde-induced DNA damage and repair in rat tracheal epithelial cells. Toxicol 51:309–320

    Article  CAS  Google Scholar 

  • Cosma GN, Jamasbi R, Marchok AC (1988) Growth inhibition and DNA damage induced by benzo[a]pyrene and formaldehyde in primary cultures of rat tracheal epithelial cells. Mutat Res 201:161–168

    PubMed  CAS  Google Scholar 

  • Dalle-Donne I, Rossi R, Giustarini D, Milzani A, Colombo R (2003) Protein carbonyl groups as biomarkers of oxidative stress. Clinica Chimica Acta 329:23–38

    Article  CAS  Google Scholar 

  • Emri G, Schaefer D, Held B, Herbst C, Zieger W, Horkay I, Bayerl C (2004) Low concentrations of formaldehyde induce DNA damage and delay DNA repair after UV irradiation in human skin cells. Exp Dermatol 13:305–315

    Article  PubMed  CAS  Google Scholar 

  • Erat M, Ciftci M (2006) Effect of melatonin on enzyme activities of glutathione reductase from human crythrocytes in vitro and from rat erythrocytes in vivo. Eur J Pharmacol 537:59–63

    Article  PubMed  CAS  Google Scholar 

  • Fagan JM, Sleczka BG., Sohar I (1999) Quantitation of oxidative damage to tissue proteins. Int J Biochem Cell Biol 31:751–757

    Article  PubMed  CAS  Google Scholar 

  • Grafström RC (1990) In vitro studies of aldehyde effects related to human respiratory carcinogenesis. Mutat Res 238:175–184

    PubMed  Google Scholar 

  • Grafström RC, Fornace AJ Jr, Autrup H, Lechner JF, Harris CC (1983) Formaldehyde damage to DNA and inhibition of DNA repair in human bronchial cells. Science 220:216–218

    Article  PubMed  Google Scholar 

  • Grafström RC, Fornace AJ Jr, Harris CC (1984) Repair of DNA damage caused by formaldehyde in human cells. Cancer Res 44:4323–4327

    PubMed  Google Scholar 

  • Heck H, Casanova M (1999) Pharmacodynamics of formaldehyde: applications of a model for the arrest of DNA replication by DNA-protein cross-links. Toxicol Appl Pharmacol 160:86–100

    Article  PubMed  CAS  Google Scholar 

  • Kim WJ, Terada N, Nomura T, Takahashi R, Lee SD, Park JH, Kinno A (2002) Effects of formaldehyde on the expression of adhesion molecules in nasal microvascular endothelial cells: the role of formaldehyde in the pathogenesis of sick building syndrome. Clin Exp Allergy 32:287–295

    Article  PubMed  CAS  Google Scholar 

  • Kita T, Fujimura M, Myou S, Ishiura Y, Abo M, Katayama N, Nishitsuji M, Yoshimi Y, Nomura S, Oribe Y, Nakao S (2003) Potentiation of allergic bronchoconstriction by repeated exposure to formaldehyde in guinea-pigs in vivo. Clin Exp Allergy 33:1747–1753

    Article  PubMed  CAS  Google Scholar 

  • Künn H, Borchert A (2002) Regulation of enzymatic lipid peroxidation: the interplay of peroxidizing and peroxide reducing enzymes. Free Rad Biol Med 33:154–172

    Article  Google Scholar 

  • Liteplo RG., Meek ME (2003) Inhaled formaldehyde: exposure estimation, hazard characterization, and exposure-response analysis. J Toxicol Environ Health Part B 6:85–114

    Article  CAS  Google Scholar 

  • Mazzetti MB, Taira MC, Lelli SM, Dascal E, Basabe JC, San Martin de Viale LC (2004) Hexachlorobenzene impairs glucose metabolism in a rat model of porphyria cutanea tarda: a mechanistic approach. Arch Toxicol 78:25–33

    Article  PubMed  CAS  Google Scholar 

  • Metz B, Kersten GFA, Hoogerhout P, Brugghe HF, Timmermans HAM, De Jong A, Meiring H, Ten Hove J, Hennink WE, Crommelin DJ, Jiskoot W (2004) Identification of formaldehyde-induced modifications in proteins: reactions with model peptides. J Biol Chem 279:6235–6243

    Article  PubMed  CAS  Google Scholar 

  • Nakazawa H, Ikeda H, Yamashita T, Hara I, Kumai Y, Endo G, Endo Y (2005) A case of sick building syndrome in a Japanese office worker. Ind Health 43:341–345

    Article  PubMed  Google Scholar 

  • Oh S, Im H, Oh E, Lee J, Khim J, Mun J, Kim Y, Lee E, Kim J, Sul D (2004) Effects of benzo(a)pyrene on protein expression in Jurkat T-cells. Proteomics 4:3514–3526

    Article  PubMed  CAS  Google Scholar 

  • Ohtsuka R, Shutoh Y, Fujie H, Yamaguchi S, Takeda M, Harada T, Doi K (2003) Rat strain difference in histology and expression of Th1- and Th2-related cytokines in nasal mucosa after short-term formaldehyde inhalation. Exp Toxicol Pathol 54:287–291

    Article  PubMed  CAS  Google Scholar 

  • Ross WE, Shipley N (1980) Relationship between DNA damage and survival in formaldehyde-treated mouse cells. Mutat Res 79:277–283

    Article  PubMed  CAS  Google Scholar 

  • Saito Y, Nishio K, Yoshida Y, Niki E (2005) Cytotoxic effect of formaldehyde with free radicals via increment of cellular reactive oxygen species. Toxicology 210:235–245

    Article  PubMed  CAS  Google Scholar 

  • Savinova OV, Matsukawa N, Smithies O, John SWM (1997) Mouse natriuretic peptide receptor 3 gene maps to proximal chromosome 15. Mamm Genome 8:788

    Article  PubMed  CAS  Google Scholar 

  • Schneider-Yin X, Szlendak U, Lipniacka AI, Minder EI, Gegor A (2006) Nine novel mutations in the hydroxymethylbilane synthase gene of polish patients with acute intermittent porphyyria. Clin Genet 69:284–286

    Article  PubMed  CAS  Google Scholar 

  • Singh NP, McCoy MT, Tice RR, Schneider EL (1988). A simple technique for quantitation of low levels of DNA damage in individual cells. Exp Cell Res 175:184–191

    Article  PubMed  CAS  Google Scholar 

  • Tang M, Xie Y, Yi Y, Wang W (2003) Effects of formaldehyde on germ cells of male mice. Wei Sheng Yan Jiu 32:544–548

    PubMed  CAS  Google Scholar 

  • The International Agency for Research on Cancer (IARC) (1995) 62:217–362

  • Thrasher JD, Wojdani A, Cheung G., Euser C (1987) Evidence for formaldehyde antibodies and altered cellular immunity in subjects exposed to formaldehyde in mobile home. Arch Environ Health 42:347–350

    Article  PubMed  CAS  Google Scholar 

  • Yoo H-W, Warner CA, Chen C-H, Desnik RJ (1993) Hydroxymethylbilane synthesis: complete genomic sequence and amplifiable polymorphisms in the human gene. Genomics 15:21–29

    Article  PubMed  CAS  Google Scholar 

  • Zhong W, Que Hee SS (2004) Formaldehyde-induced DNA adducts as biomarkers of in vitro human nasal epithelial cell exposure to formaldehyde. Mutat Res 563:13–24

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This research was supported by the grant of Medical Research Center for Environmental Toxico-Genomics and Proteomics and funded by Korea Science and Engineering Foundations and ministry of Science and Technology and by the Ministry of Environment as “The Eco-Technopia 21 project”.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Donggeun Sul.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sul, D., Kim, H., Oh, E. et al. Gene expression profiling in lung tissues from rats exposed to formaldehyde. Arch Toxicol 81, 589–597 (2007). https://doi.org/10.1007/s00204-007-0182-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00204-007-0182-9

Keywords

Navigation