Linked Life Data

12688418

Source:http://linkedlifedata.com/resource/pubmed/id/12688418

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2003-4-11
pubmed:abstractText
Tobacco smoke, recognized as a major etiological factor for cancers of the upper aerodigestive tract, represents an abundant source of reactive oxygen species (ROS), which are believed to play a significant role in mutagenesis and carcinogenesis. An additional source of ROS in tissues exposed to tobacco smoke may be metabolic oxidation of polycyclic aromatic hydrocarbons (PAH). To investigate the relationships between oxidative DNA lesions and aromatic DNA adducts, six modified DNA bases 5-hydroxyuracil, 5-hydroxycytosine, 7,8-dihydro-8-oxoguanine, 7,8-dihydro-8-oxoadenine, 2,6-diamino-4-hydroxy-5-formamidopyrimidine and 4,6-diamino-5-formamidopyrimidine and the total level of PAH-related DNA adducts were measured in cancerous and the surrounding normal larynx tissues (68 subjects), using gas chromatography/isotope-dilution mass spectroscopy with selected ion monitoring and the 32P-postlabeling-HPLC assay, respectively. The levels of oxidative DNA lesions in cancerous and adjacent tissue were comparable; the differences between the two types of tissue were significant only for 5-hydroxypyrimidines (slightly higher levels were observed in the adjacent tissue). Comparable levels of DNA lesions in cancerous and the surrounding normal tissues observed in the larynx tumors support a field cancerization theory. The surrounding tissues may still be recognized as normal by histological criteria. However, molecular alterations resulting from the chronic tobacco smoke exposure, which equally affects larynx epithelia, may lead to multiple premalignant lesions. Thus, a demonstration of similar levels of DNA damage in cancerous and the adjacent tissue could explain a frequent formation of secondary tumors in the larynx and the frequent recurrence in this type of cancer. A weak, but distinct effect of tumor grading and metastatic status was observed in both kinds of tissue in the case of 5-hydroxyuracil, 5-hydroxycytosine, 7,8-dihydro-8-oxoguanine, 7,8-dihydro-8-oxoadenine. This effect was displayed as a gradual shift in the data distribution toward high values from G1 through G2-G3 and from non-metastatic to metastatic tumors. Since the levels of oxidative DNA base modifications tended to increase with the tumor aggressiveness, we postulate that the oxidative DNA lesions increase genetic instability and thus contribute to tumor progression in laryngeal cancer. No associations between aromatic adduct levels and oxidative DNA lesions were present, suggesting that the metabolism of PAH does not contribute significantly to the oxidative stress in larynx tissues, remaining the tobacco smoke ROS as a major source of oxidative DNA damage in the exposed tissue.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1071-5762
pubmed:author
pubmed:issnType
Print
pubmed:volume
37
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
231-40
pubmed:dateRevised
2006-12-5
pubmed:meshHeading
pubmed-meshheading:12688418-Adult, pubmed-meshheading:12688418-Aged, pubmed-meshheading:12688418-Aged, 80 and over, pubmed-meshheading:12688418-Carcinoma, Squamous Cell, pubmed-meshheading:12688418-Chromatography, High Pressure Liquid, pubmed-meshheading:12688418-DNA, pubmed-meshheading:12688418-DNA Adducts, pubmed-meshheading:12688418-DNA Damage, pubmed-meshheading:12688418-Disease Progression, pubmed-meshheading:12688418-Female, pubmed-meshheading:12688418-Gas Chromatography-Mass Spectrometry, pubmed-meshheading:12688418-Humans, pubmed-meshheading:12688418-Laryngeal Neoplasms, pubmed-meshheading:12688418-Larynx, pubmed-meshheading:12688418-Male, pubmed-meshheading:12688418-Middle Aged, pubmed-meshheading:12688418-Oxygen, pubmed-meshheading:12688418-Polycyclic Hydrocarbons, Aromatic, pubmed-meshheading:12688418-Reactive Oxygen Species, pubmed-meshheading:12688418-Tobacco
pubmed:year
2003
pubmed:articleTitle
Oxidative DNA base modifications and polycyclic aromatic hydrocarbon DNA adducts in squamous cell carcinoma of larynx.
pubmed:affiliation
Polish Academy of Sciences, Institute of Human Genetics, Strzeszy?ska 32, 60-479 Pozna?, Poland. japawel@man.poznan.pl
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't