Identification of formaldehyde-responsive genes by suppression subtractive hybridization.
Formaldehyde is frequently used in indoor household and occupational environments. Inhalation of formaldehyde invokes an inflammatory response, including a variety of allergic signs and symptoms. Therefore, formaldehyde has been considered as the most prevalent cause of sick building syndrome, which has become a major social problem, especially in developing urban areas. Further formaldehyde is classified as a genotoxicant in the respiratory tract of rats and humans. To better understand the molecular mechanisms involved in formaldehyde intoxication, we sought differentially regulated genes by formaldehyde exposure to Hs 680.Tr human trachea cells, using polymerase chain reaction (PCR)-based suppression subtractive hybridization. We identified 27 different formaldehyde-inducible genes, including those coding for the major histocompatibility complex, class IA, calcyclin, glutathione S-transferase pi, mouse double minute 2 (MDM2), platelet-derived growth factor receptor alpha, and which are known to be associated with cell proliferation and differentiation, immunity and inflammation, and detoxification. Induction of these genes by formaldehyde treatment was confirmed by reverse transcription PCR and western blot analysis. Further, the expression of calcyclin, glutathione S-transferase pi, PDGFRA and MDM2 were significantly induced in the tracheal epithelium of Sprague Dawley rats after formaldehyde inhalation. Our results suggest that the elevated levels of these genes may be associated with the formaldehyde-induced toxicity, and that they deserve evaluation as potential biomarkers for formaldehyde intoxication.
College of Pharmacy, Seoul National University, Seoul 151-742, South Korea.
Min-Ho
MH
Lee
Young-Ae
YA
Kim
Tae-Young
TY
Na
Sung-Hye
SH
Kim
Young Kee
YK
Shin
Byung-Hoon
BH
Lee
Ho-Sang
HS
Shin
Mi-Ock
MO
Lee
D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D005557:Formaldehyde / Q000633:toxicity*; D015870:Gene Expression / Q000187:drug effects*; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008969:Molecular Sequence Data; D009693:Nucleic Acid Hybridization / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D020545:Respiratory Mucosa / Q000187:drug effects / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014132:Trachea / Q000187:drug effects* / Q000378:metabolism
D000393:Air Pollutants; D005557:Formaldehyde