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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2002-12-10
pubmed:abstractText
11Beta-hydroxysteroid dehydrogenase 1 (11beta-HSD1) has been identified as a major detoxification enzyme of one of the most potent tobacco smoke-derived carcinogens, NNK. If not metabolized by 11beta-HSD1, activation of NNK by cytochrome p450 mono-oxidase 2D6 (CYP2D6) results in an electrophile intermediate responsible for DNA damage. Interindividual variability in the expression of 11beta-HSD1 and CYP2D6 has been found to influence the susceptibility to lung cancer. The aim of this study was to compare 11beta-HSD1 mRNA expression and CYP2D6 metabolizer status in pharyngeal tissues of patients with oropharyngeal carcinoma and controls. In 20 patients with oropharyngeal cancer and 15 non-smoking controls, the 11beta-HSD1 mRNA expression was assessed with RT-PCR. The frequency of genetic polymorphisms of the CYP2D6 gene was assessed using RFLP. It was found that 11beta-HSD1 mRNA is expressed in human pharyngeal mucosa. It is upregulated in mucosa exposed to tobacco smoke. In tumour tissues, 11beta-HSD1 expression was significantly lower than in non-affected mucosa. The frequency distribution of CYP2D6 gene polymorphisms was similar in patients and controls. Chronic tobacco abuse results in 11beta-HSD1 enzyme induction. A reduction of 11beta-HSD1 expression in tumour tissues could be a consequence of malignantly transformed cells. It remains unclear if the lower 11beta-HSD1 expression gives rise to an increased rate of additional mutations.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0307-7772
pubmed:author
pubmed:issnType
Print
pubmed:volume
27
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
453-7
pubmed:dateRevised
2005-5-2
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
11Beta-hydroxysteroid dehydrogenase 1 expression in squamous cell carcinomas of the head and neck.
pubmed:affiliation
Department of Otorhinolaryngology, University of Ulm, Germany. silke.gronau@medizin.uni-ulm.de
pubmed:publicationType
Journal Article