LIVIVO - The Search Portal for Life Sciences

zur deutschen Oberfläche wechseln
Advanced search

Search results

Result 1 - 4 of total 4

Search options

  1. Article ; Online: The critical DNA damage by benzo(a)pyrene in lung tissues of smokers and approaches to preventing its formation.

    Alexandrov, Kroum / Rojas, Margarita / Satarug, Soisungwan

    Toxicology letters

    2010  Volume 198, Issue 1, Page(s) 63–68

    Abstract: Benzo(a)pyrene (BP) and cadmium are environmental pollutants found in foodstuffs, cigarette smoke, and polluted air. BP is converted in liver and lung to benzo(a)pyrene-7,8-diol-9,10-epoxide (BPDE) by the enzymes of the cytochrome P450 (CYP) superfamily, ...

    Abstract Benzo(a)pyrene (BP) and cadmium are environmental pollutants found in foodstuffs, cigarette smoke, and polluted air. BP is converted in liver and lung to benzo(a)pyrene-7,8-diol-9,10-epoxide (BPDE) by the enzymes of the cytochrome P450 (CYP) superfamily, namely CYP1A1/1A2, and CYP1B1. BPDE reacts with DNA primarily at the N(2)-position of guanine, producing benzo(a)pyrene-7,8-diol-9,10-epoxide-N(2)-deoxyguanosine (BPDE-dG) adduct. BPDE reacts with DNA also at N(6) position of adenine, producing the minor N(6)-deoxyadenosine adduct, but BPDE-dG adduct is a well-established risk factor for lung cancer. We thus argue that BPDE-dG adduct could be used as a model biomarker in searching and validating of approaches to reducing lung cancer risk. If the formation of BPDE-dG adduct were to be inhibited or blocked in bronchial epithelial cells, so could lung cancer development. The best way to lower BPDE-dG formation in the lung is to stop smoking. However, the following approaches could also be considered for highly addicted smokers: (a) decrease BP and cadmium intake from food, cigarettes and other environmental sources; (b) avoid meat and other food high in BP and cadmium; (c) decrease the CYP-mediated conversion of BP in liver and lung; (d) lower free radicals and cadmium in cigarette smoke; and (e) increase BPDE detoxification.
    MeSH term(s) Benzo(a)pyrene/toxicity ; Cadmium/toxicity ; Carcinogens, Environmental/toxicity ; Cytochrome P-450 Enzyme System/metabolism ; DNA Damage ; Environmental Exposure/statistics & numerical data ; Free Radicals/metabolism ; Liver/metabolism ; Lung/drug effects ; Lung/metabolism ; Lung Neoplasms/chemically induced ; Lung Neoplasms/epidemiology ; Lung Neoplasms/metabolism ; Risk Factors ; Smoking/adverse effects
    Chemical Substances Carcinogens, Environmental ; Free Radicals ; Cadmium (00BH33GNGH) ; Benzo(a)pyrene (3417WMA06D) ; Cytochrome P-450 Enzyme System (9035-51-2)
    Language English
    Publishing date 2010-09-15
    Publishing country Netherlands
    Document type Journal Article ; Review
    ZDB-ID 433788-8
    ISSN 1879-3169 ; 0378-4274
    ISSN (online) 1879-3169
    ISSN 0378-4274
    DOI 10.1016/j.toxlet.2010.04.009
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 1367: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  2. Article: DNA damage by benzo(a)pyrene in human cells is increased by cigarette smoke and decreased by a filter containing rosemary extract, which lowers free radicals.

    Alexandrov, Kroum / Rojas, Margarita / Rolando, Christian

    Cancer research

    2006  Volume 66, Issue 24, Page(s) 11938–11945

    Abstract: We found previously that the human lung benzo(a)pyrene (BP)-7,8-diol-9,10-epoxide-N(2)-deoxyguanosine (BPDE-dG) adduct concentrate in the target bronchial cells. This adduct is now considered to be critical event in tumorigenesis by BP. In this study, we ...

    Abstract We found previously that the human lung benzo(a)pyrene (BP)-7,8-diol-9,10-epoxide-N(2)-deoxyguanosine (BPDE-dG) adduct concentrate in the target bronchial cells. This adduct is now considered to be critical event in tumorigenesis by BP. In this study, we investigate the contribution of cigarette smoke on the BPDE-dG formation. In a cell-free system, the amount of (-)-anti-BPDE-dG adduct increased linearly with concentration of cigarette smoke in the presence of (+)-BP-7,8-diol. Catalase and superoxide dismutase inhibited its formation by >80%. When MCF-7 cells were treated for 2 hours with the (+)-BP-7,8-diol, cigarette smoke increased dose dependently the formation of (-)-anti-BPDE-dG and decreased the cytochrome P450 (CYP)-dependent formation of (+)-r-7,t-8-dihydroxy-c-9,10-oxy-7,8,9,10-tetrahydro-BP the adduct. Then, cells were treated for up to 1 day with BP and then exposed for 2 hours with cigarette smoke. During these 2 hours, there are twice the increase in the adduct formation in cells treated with cigarette smoke compared with levels in nontreated cells due to CYP activity. Thus, cigarette smoke containing reactive oxygen species may activate the second step of BP metabolic way, leading to the formation of BPDE-dG adduct. Cigarette smoke thus seems may be in part responsible for the formation of the critical lung tumorigenic adduct. Finally, modified cigarette filter containing rosemary extract decreases by >70% of the BPDE-dG adducts level due to the cigarette smoke in MCF-7 cells. This approach may lead to decreasing lung cancer risk in addicted smokers.
    MeSH term(s) Benzo(a)pyrene/antagonists & inhibitors ; Benzo(a)pyrene/toxicity ; Breast Neoplasms ; Cell Line, Tumor ; DNA/drug effects ; DNA Damage ; DNA, Neoplasm/drug effects ; Female ; Filtration ; Free Radicals/metabolism ; Humans ; Plant Extracts/pharmacology ; Powders ; Rosmarinus ; Smoke/adverse effects
    Chemical Substances DNA, Neoplasm ; Free Radicals ; Plant Extracts ; Powders ; Smoke ; Benzo(a)pyrene (3417WMA06D) ; DNA (9007-49-2)
    Language English
    Publishing date 2006-12-15
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1432-1
    ISSN 1538-7445 ; 0008-5472
    ISSN (online) 1538-7445
    ISSN 0008-5472
    DOI 10.1158/0008-5472.CAN-06-3277
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Uh III Zs.135/5: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  3. Article: CYP1A1 and GSTM1 genotypes affect benzo[a]pyrene DNA adducts in smokers' lung: comparison with aromatic/hydrophobic adduct formation.

    Alexandrov, Kroum / Cascorbi, Ingolf / Rojas, Margarita / Bouvier, Guy / Kriek, Erik / Bartsch, Helmut

    Carcinogenesis

    2002  Volume 23, Issue 12, Page(s) 1969–1977

    Abstract: Benzo[a]pyrene diol epoxide (BPDE)-DNA adducts are involved in the induction of p53 mutations and probably in the causation of human lung cancer associated with cigarette smoking. The ratio between CYP1A1 and GST enzyme activities is a critical ... ...

    Abstract Benzo[a]pyrene diol epoxide (BPDE)-DNA adducts are involved in the induction of p53 mutations and probably in the causation of human lung cancer associated with cigarette smoking. The ratio between CYP1A1 and GST enzyme activities is a critical determinant of the target dose of carcinogenic BPDE and other DNA-reactive PAH metabolites. In this review, we summarize the published data on modulation of (+)-anti-BPDE-DNA adduct levels in smokers' lungs by CYP1A1*2 genotypes alone or in combination with GSTM1 polymorphism and compare these results with those reported for aromatic/hydrophobic (bulky) DNA adducts. The data published so far show only a trend for a non-significant increase in bulky DNA adduct levels in subjects with GSTM1*0 or the CYP1A1*2-GSTM1*0 genotype combination. In contrast, a clear dependence of (+)-anti-BPDE-DNA adduct levels was found as a function of the CYP1A1 and GSTM1 genotypes: In lung parenchyma, this adduct was more pronounced in persons with the GSTM1*0 genotype, and CYP1A1*2-GSTM1*0 carriers had higher (+)-anti-BPDE-DNA adduct levels than those with CYP1A1*1/*1-GSTM1*0. The homozygous CYP1A1*2/*2 carriers in the GSTM1*0 group had the highest (+)-anti-BPDE-DNA adduct levels. Our analysis leads to the conclusion that the risk-modifying effects of metabolic genotypes and of gene interactions might be more easily identifiable if specific markers of structurally defined adducts were used, such as the (+)-anti-BPDE-DNA adduct. These results are also consistent with the hypothesis that BP (PAH) induce G:C to T:A transversion mutations in the hotspot codons of the p53 tumor suppressor gene and are thus involved in malignant transformation of the lung tissue of smokers.
    MeSH term(s) Benzo(a)pyrene/metabolism ; Carcinogens ; Cytochrome P-450 CYP1A1/genetics ; DNA Adducts/metabolism ; Female ; Genes, p53 ; Genotype ; Glutathione Transferase/genetics ; Glutathione Transferase/metabolism ; Humans ; Lung/drug effects ; Lung/pathology ; Male ; Mutation ; Smoking
    Chemical Substances Carcinogens ; DNA Adducts ; Benzo(a)pyrene (3417WMA06D) ; Cytochrome P-450 CYP1A1 (EC 1.14.14.1) ; Glutathione Transferase (EC 2.5.1.18) ; glutathione S-transferase M1 (EC 2.5.1.18)
    Language English
    Publishing date 2002-12
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 603134-1
    ISSN 1460-2180 ; 0143-3334
    ISSN (online) 1460-2180
    ISSN 0143-3334
    DOI 10.1093/carcin/23.12.1969
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 1558: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  4. Article: 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.

    Rojas, Margarita / Marie, Beatrice / Vignaud, Jean Michel / Martinet, Nadine / Siat, Joëlle / Grosdidier, Gilles / Cascorbi, Ingolf / Alexandrov, Kroum

    Cancer letters

    2004  Volume 207, Issue 2, Page(s) 157–163

    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 ... ...

    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.
    MeSH term(s) 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide/analogs & derivatives ; 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide/metabolism ; 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide/toxicity ; Adenocarcinoma/genetics ; Adenocarcinoma/metabolism ; Adenocarcinoma/pathology ; Adult ; Aged ; Aged, 80 and over ; Bronchi/drug effects ; Bronchi/metabolism ; Carcinogens/toxicity ; Carcinoma, Large Cell/genetics ; Carcinoma, Large Cell/metabolism ; Carcinoma, Large Cell/pathology ; Carcinoma, Squamous Cell/genetics ; Carcinoma, Squamous Cell/metabolism ; Carcinoma, Squamous Cell/pathology ; DNA Adducts ; DNA Damage ; DNA Repair ; DNA, Neoplasm/drug effects ; Deoxyguanosine/analogs & derivatives ; Deoxyguanosine/metabolism ; Epithelial Cells/drug effects ; Epithelial Cells/metabolism ; Female ; Humans ; Lung Neoplasms/genetics ; Lung Neoplasms/metabolism ; Lung Neoplasms/pathology ; Male ; Middle Aged
    Chemical Substances Carcinogens ; DNA Adducts ; DNA, Neoplasm ; 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide (55097-80-8) ; 7,8-dihydroxy-9,10-epoxide-7,8,9,10-tetrahydrobenzo(a)pyrene-10-deoxyguanosine (62698-04-8) ; Deoxyguanosine (G9481N71RO)
    Language English
    Publishing date 2004-04-30
    Publishing country Ireland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 195674-7
    ISSN 1872-7980 ; 0304-3835
    ISSN (online) 1872-7980
    ISSN 0304-3835
    DOI 10.1016/j.canlet.2003.11.016
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 1177: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

To top