Gene expression profiling in lung tissues from rats exposed to formaldehyde.
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.
Sul
Donggeun
D
Graduate School of Medicine, Korea University, Anamdong 5 Ka, Sungbukku, Seoul, 136-701, South Korea. dsul@korea.ac.kr
Kim
Hyunsook
H
Oh
Eunha
E
Phark
Sohee
S
Cho
Eunkyung
E
Choi
Seonyoung
S
Kang
Hyung-Sik
HS
Kim
Eun-Mi
EM
Hwang
Kwang-Woo
KW
Jung
Woon-Won
WW
D000818:Animals; D002273:Carcinogens / Q000633:toxicity; D004249:DNA Damage; D005557:Formaldehyde / Q000633:toxicity*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D015227:Lipid Peroxidation; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009153:Mutagens / Q000633:toxicity; D050050:Protein Carbonylation; D051381:Rats; D017207:Rats, Sprague-Dawley
D002273:Carcinogens; D009153:Mutagens; D005557:Formaldehyde; D008315:Malondialdehyde