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FORMALDEHYDE-INDUCED GENE EXPRESSION IN F344 RAT NASAL RESPIRATORY EPITHELIUM.
Hester, S D., G. B. Benavides, L. Yoon, K. T. Morgan, F. Zou, W. Barry, AND D C. Wolf. FORMALDEHYDE-INDUCED GENE EXPRESSION IN F344 RAT NASAL RESPIRATORY EPITHELIUM. TOXICOLOGY 187(1):13-24, (2003).
Formaldehyde-induced gene expression in F344 rat nasal respiratory epithelium
Formaldehyde, an occupational and environmental toxicant used extensively in the manufacturing of many household and personal use products, is known to induce squamous cell carcinomas in the nasal turbinates of rats and mice and squamous metaplasia in monkey noses. Tissue responses to formaldehyde include a dose dependent epithelial degeneration, respiratory cell hypertrophy, and squamous metaplasia. The primary target for chemical toxicity in both rodents and monkeys is the respiratory nasal epithelium. Formaldehyde increases nasal epithelial cell proliferation and DNA-protein crosslinks that are associated with subsequent nasal cancer development. To address the acute effects of formaldehyde exposure that might contribute to known pathological changes, cDNA gene expression analysis was used. Two groups of male F344 rats received either 40 ul of distilled water or formaldehyde (400 mM ) infused into each nostril. After 24 hrs following treatment, nasal epithelium was recovered from which total RNA was used to generate cDNA probes. Significance Analysis of Microarrays (SAM) analysis using data from Clontech TM Rat Atlas 1.2 arrays revealed that 24 of the 1185 genes queried were significantly up-regulated and 22 genes were significantly downregulated. Ten of the differentially expressed genes were confirmed by quantitative real time RT PCR. Functional gene categories altered included xenobiotic metabolism, cell cycle, apoptosis, and DNA repair. These data reveal that multiple pathways are dysregulated including two critical processes, cell proliferation and DNA synthesis/repair. Differential gene expression profiles may provide clues that could be used to define mechanisms involved in formaldehyde-induced nasal cancer.
Record Details:Record Type: DOCUMENT (JOURNAL/PEER REVIEWED JOURNAL)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LABORATORY
ENVIRONMENTAL CARCINOGENESIS DIVISION
CANCER BIOLOGY BRANCH