title: Decreased repair activities of 1,N(6)-ethenoadenine and 3,N(4)-ethenocytosine in lung adenocarcinoma patients.
abstract: To assess the role of oxidative stress and lipid peroxidation (LPO) in the pathogenesis of lung cancer, we measured the levels of 1,N(6)-ethenoadenine (epsilonA) and 3,N(4)-ethenocytosine (epsilonC) in the DNA by immunoaffinity/(32)P postlabeling (33 cases). We also measured the capacity for epsilonA and epsilonC repair (by the nicking assay) in normal and tumor lung tissues, as well as in blood leukocytes of lung cancer patients (56 cases). Repair activities for epsilonA and epsilonC were also assayed in leukocytes of healthy volunteers, matched with cancer patients for age, sex, and smoking habit (25 individuals). Up to 10-fold variations among individuals were observed both in adducts level and repair activities. No differences in epsilonA and epsilonC levels between tumor and nonaffected lung tissues were recorded. However, leukocytes accumulated a significantly higher number of DNA adducts than the lung tissues. Repair activities for both epsilonA and epsilonC were significantly higher in tumor than in normal lung tissue. No significant differences in epsilonA and epsilonC repair activities were associated with age, sex, or smoking habit. However, a significant difference in repair capacity was observed between two histological types of lung cancer, squamous cell carcinoma (SQ) and adenocarcinoma (AD). In individuals suffering from lung AD, epsilonA- and epsilonC-repair activities in normal lung and blood leukocytes were significantly lower than in SQ patients. Moreover, in nonaffected lung tissue of AD patients, the ratio epsilonA/epsilonC adducts was lower than in SQ patients. Differences have also been found between epsilonA and epsilonC repair activities of cancer patients and healthy volunteers. Repair capacity for epsilonA was significantly lower in blood leukocytes of lung cancer patients than in leukocytes of healthy volunteers (P = 0.012). This difference was even larger between healthy volunteers and patients developing inflammation-related AD (P = 0.00033). Repair activities for epsilonC were the same in leukocytes of healthy controls, all lung cancer patients, and SQ patients. However, individuals with ADs revealed significantly lower epsilonC-repair activity (P = 0.013). These results suggest that oxidative stress-mediated lipid peroxidation might contribute to induction and/or progression of lung cancer. Decreased activity of base excision repair pathway for epsilonA and epsilonC is associated particularly with inflammation-related lung AD.
authors.affiliation: Department of Molecular Biology, Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawińskiego 5a, 02-106 Warsaw, Poland.
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Speina
authors.forename: Maja
authors.initials: M
authors.lastname: Zielińska
authors.forename: Alain
authors.initials: A
authors.lastname: Barbin
authors.forename: Daniel
authors.initials: D
authors.lastname: Gackowski
authors.forename: Janusz
authors.initials: J
authors.lastname: Kowalewski
authors.forename: Maria A
authors.initials: MA
authors.lastname: Graziewicz
authors.forename: Janusz A
authors.initials: JA
authors.lastname: Siedlecki
authors.forename: Ryszard
authors.initials: R
authors.lastname: Oliński
authors.forename: Barbara
authors.initials: B
authors.lastname: Tudek
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000378:metabolism*; D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D000367:Age Factors; D000368:Aged; D003596:Cytosine / Q000031:analogs & derivatives* / Q000378:metabolism*; D018736:DNA Adducts / Q000378:metabolism; D004260:DNA Repair; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D007962:Leukocytes / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012737:Sex Factors; D012907:Smoking / Q000235:genetics / Q000378:metabolism
chemical_list: D018736:DNA Adducts; D004273:DNA, Neoplasm; C004981:1,N(6)-ethenoadenine; C051143:3,N(4)-ethanocytosine; D003596:Cytosine; D000225:Adenine