title: High DNA damage by benzo[a]pyrene 7,8-diol-9,10-epoxide in bronchial epithelial cells from patients with lung cancer: comparison with lung parenchyma.
abstract: In the present study, the level of benzo[a]pyrene 7,8-diol-9,10-epoxide-N(2)-deoxyguanosine (BPDE-N(2)-dG) in normal bronchial epithelial cells from non-cancerous bronchus of 22 lung cancer subjects was evaluated and compared to the lung parenchyma. We found very high formation of BPDE-N(2)-dG adduct in samples corresponding to a pure preparation of bronchial epithelial cells with 4-fold interindividual differences in the DNA adduct levels in the range of 36.5-175.4 BPDE-N(2)-dG adducts/10(8) nucleotides in smokers (mean: 84.7+/-38.4; n = 13) and 3-fold differences in the range of 19.7-62.4 in non-smokers (mean: 37.6+/-22.2; n = 3). DNA isolated from the bronchial tissue consisting of bronchial lining epithelium with adjacent lamina propria showed significantly lower BPDE-N(2)-dG formation (P < 0.001) in the range of 0.4-4.2 BPDE-N(2)-dG adducts/10(8) nucleotides (mean: 1.8+/-0.56; n = 6). This difference is clearly related to the procedure used to prepare the bronchial tissue samples leading to the presence of different types of cells. Eight samples from the normal parenchyma did not show measurable adducts, the other 14 samples showed 50-fold variation (mean: 1.7+/-1.5; range 0.1-5.2 adducts/10(8) nucleotides; n = 14). There were considerably higher adduct levels in pure bronchial epithelial cells than in parenchymal tissue (75.8+/-38.8 vs 0.9+/-1.5 adducts/10(8) nucleotides) (P < 0.0002) BPDE-N(2)-dG adduct concentrate almost exclusively in bronchial epithelial cells. The adduct values obtained in bronchial epithelial cells could be considered as 'critical' for the initiation of human lung cancer. The high formation of BPDE-N(2)-dG adducts in bronchial epithelial cells and investigations showing that the profile of mutations induced by BPDE in these cells is similar to that seen in the p53 gene isolated from human lung tumors implicates benzo[a]pyrene as important carcinogen in tobacco-induced lung cancer in human beings.
authors.affiliation: EA3443 and Laboratoire d'Anatomie Pathologique, Faculté de Médecine, Université de Nancy, Av. de La Forêt de Haye, Vandoeuvre-Les-Nancy 54500, France.
authors.forename: Margarita
authors.initials: M
authors.lastname: Rojas
authors.forename: Beatrice
authors.initials: B
authors.lastname: Marie
authors.forename: Jean Michel
authors.initials: JM
authors.lastname: Vignaud
authors.forename: Nadine
authors.initials: N
authors.lastname: Martinet
authors.forename: Joëlle
authors.initials: J
authors.lastname: Siat
authors.forename: Gilles
authors.initials: G
authors.lastname: Grosdidier
authors.forename: Ingolf
authors.initials: I
authors.lastname: Cascorbi
authors.forename: Kroum
authors.initials: K
authors.lastname: Alexandrov
mesh_terms: D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / Q000031:analogs & derivatives* / Q000378:metabolism / Q000633:toxicity*; D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001980:Bronchi / Q000187:drug effects* / Q000378:metabolism; D002273:Carcinogens / Q000633:toxicity*; D018287:Carcinoma, Large Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018736:DNA Adducts; D004249:DNA Damage; D004260:DNA Repair; D004273:DNA, Neoplasm / Q000187:drug effects*; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged
chemical_list: D002273:Carcinogens; D018736:DNA Adducts; D004273:DNA, Neoplasm; D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; C040060:7,8-dihydroxy-9,10-epoxide-7,8,9,10-tetrahydrobenzo(a)pyrene-10-deoxyguanosine; D003849:Deoxyguanosine