Identification of gene markers for formaldehyde exposure in humans.
BACKGROUND
Formaldehyde (FA) is classified as a human carcinogen and has been linked to increased leukemia rates in some epidemiologic studies. Inhalation of FA induces sensory irritation at relatively low concentrations. However, little is known concerning the cellular alterations observed after FA exposure in humans.


OBJECTIVE
Our aim was to profile global gene expression in Hs 680.Tr human tracheal fibroblasts exposed to FA and to develop biomarkers for the evaluation of FA exposure in humans.


RESULTS
We used gene expression analysis, and identified 54 genes designated as FA responsive. On the basis of these data, we conducted an exploratory analysis of the expression of these genes in human subjects exposed to high or low levels of FA. We monitored FA exposure by measuring the urinary concentration of thiazolidine-4-carboxylate (TZCA), a stable and quantitative cysteinyl adduct of FA. Nine genes were selected for real-time PCR analysis; of these, BHLHB2, CCNL1, SE20-4, C8FW, PLK2, and SGK showed elevated expression in subjects with high concentrations of TZCA.


CONCLUSIONS
The identification of gene marker candidates in vitro using microarray analysis and their validation using human samples obtained from exposed subjects is a good tool for discovering genes of potential mechanistic interest and biomarkers of exposure. Thus, these genes are differentially expressed in response to FA and are potential effect biomarkers of FA exposure.
Li
Guang-Yong
GY
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea.
Lee
Hye-Young
HY
Shin
Ho-Sang
HS
Kim
Hyeon-Young
HY
Lim
Cheol-Hong
CH
Lee
Byung-Hoon
BH
D051792:Basic Helix-Loop-Helix Proteins / Q000187:drug effects / Q000235:genetics; D015415:Biomarkers; D002460:Cell Line; D003185:Complement C8 / Q000187:drug effects / Q000235:genetics; D016213:Cyclins / Q000187:drug effects / Q000235:genetics; D004268:DNA-Binding Proteins; D004781:Environmental Exposure; D005347:Fibroblasts / Q000187:drug effects*; D005557:Formaldehyde / Q000009:adverse effects* / Q000378:metabolism; D020869:Gene Expression Profiling; D018398:Homeodomain Proteins / Q000187:drug effects / Q000235:genetics; D006801:Humans; D017874:Immediate-Early Proteins / Q000187:drug effects / Q000235:genetics; D009687:Nuclear Proteins / Q000187:drug effects / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D017346:Protein Serine-Threonine Kinases / Q000187:drug effects / Q000235:genetics; D053778:Thiazolidines / Q000652:urine; D000099184:Serum-Glucocorticoid Regulated Kinases
D051792:Basic Helix-Loop-Helix Proteins; D015415:Biomarkers; D003185:Complement C8; D016213:Cyclins; D004268:DNA-Binding Proteins; D005557:Formaldehyde; D018398:Homeodomain Proteins; D017874:Immediate-Early Proteins; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases; D053778:Thiazolidines; D000099184:Serum-Glucocorticoid Regulated Kinases; C107989:BHLHE40 protein, human; C087169:C8G protein, human; C468873:CCNL1 protein, human; C432963:TSPYL2 protein, human; C003438:thiazolidine-4-carboxylic acid