Smoking and benzo(a)pyrene-diol-epoxide DNA adducts in spermatozoa: In smokers, swim-up procedure selects spermatozoa with decreased DNA damage

2011 ◽  
Vol 205 ◽  
pp. S253-S254
Author(s):  
V. Tassistro ◽  
J. Perrin ◽  
M. Mandon ◽  
C. Metzler-Guillemain ◽  
B. Courbiere ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Adducts ◽  
Diol Epoxide

Tobacco consumption and benzo(a)pyrene-diol-epoxide–DNA adducts in spermatozoa: in smokers, swim-up procedure selects spermatozoa with decreased DNA damage

2011 ◽  
Vol 95 (6) ◽  
pp. 2013-2017 ◽  
Author(s):  
Jeanne Perrin ◽  
Virginie Tassistro ◽  
Marion Mandon ◽  
Jean-Marie Grillo ◽  
Alain Botta ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Adducts ◽  
Tobacco Consumption ◽  
Diol Epoxide

scholarly journals Identification of New Markers of Alcohol-Derived DNA Damage in Humans

Biomolecules ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 366
Author(s):  
Valeria Guidolin ◽  
Erik S. Carlson ◽  
Andrea Carrà ◽  
Peter W. Villalta ◽  
Laura A. Maertens ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Adducts ◽  
Neutral Loss ◽  
Alcohol Exposure ◽  
Dose Dependence ◽  
Accurate Mass ◽  
Constant Neutral Loss ◽  
Covalent Modifications ◽  
Underlying Mechanisms

Alcohol consumption is a risk factor for the development of several cancers, including those of the head and neck and the esophagus. The underlying mechanisms of alcohol-induced carcinogenesis remain unclear; however, at these sites, alcohol-derived acetaldehyde seems to play a major role. By reacting with DNA, acetaldehyde generates covalent modifications (adducts) that can lead to mutations. Previous studies have shown a dose dependence between levels of a major acetaldehyde-derived DNA adduct and alcohol exposure in oral-cell DNA. The goal of this study was to optimize a mass spectrometry (MS)-based DNA adductomic approach to screen for all acetaldehyde-derived DNA adducts to more comprehensively characterize the genotoxic effects of acetaldehyde in humans. A high-resolution/-accurate-mass data-dependent constant-neutral-loss-MS3 methodology was developed to profile acetaldehyde-DNA adducts in purified DNA. This resulted in the identification of 22 DNA adducts. In addition to the expected N2-ethyldeoxyguanosine (after NaBH3CN reduction), two previously unreported adducts showed prominent signals in the mass spectra. MSn fragmentation spectra and accurate mass were used to hypothesize the structure of the two new adducts, which were then identified as N6-ethyldeoxyadenosine and N4-ethyldeoxycytidine by comparison with synthesized standards. These adducts were quantified in DNA isolated from oral cells collected from volunteers exposed to alcohol, revealing a significant increase after the exposure. In addition, 17 of the adducts identified in vitro were detected in these samples confirming our ability to more comprehensively characterize the DNA damage deriving from alcohol exposures.

Overexpression of Stably Transfected Human Glutathione S-Transferase P1–1 Protects against DNA Damage by Benzo[a]pyrene Diol-Epoxide in Human T47D Cells

1998 ◽  
Vol 54 (2) ◽  
pp. 298-304 ◽  
Author(s):  
Wanda R. Fields ◽  
Charles S. Morrow ◽  
Amanda J. Doss ◽  
Kathrin Sundberg ◽  
Bengt Jernström ◽  
...  
Keyword(s):  
Dna Damage ◽  
Glutathione S Transferase ◽  
T47d Cells ◽  
Diol Epoxide

Oxidative DNA damage and aromatic DNA adducts in patients with colorectal cancer in Egypt

2000 ◽  
Vol 118 (4) ◽  
pp. A1097
Author(s):  
Amr S. Soliman ◽  
Donghui Li ◽  
Melissa L. Bondy ◽  
Bernard Levin
Keyword(s):  
Colorectal Cancer ◽  
Dna Damage ◽  
Dna Adducts ◽  
Oxidative Dna Damage

scholarly journals Tobacco-Specific Carcinogens Induce Hypermethylation, DNA Adducts, and DNA Damage in Bladder Cancer

2017 ◽  
Vol 10 (10) ◽  
pp. 588-597 ◽  
Author(s):  
Feng Jin ◽  
Jose Thaiparambil ◽  
Sri Ramya Donepudi ◽  
Venkatrao Vantaku ◽  
Danthasinghe Waduge Badrajee Piyarathna ◽  
...  
Keyword(s):  
Dna Damage ◽  
Bladder Cancer ◽  
Dna Adducts

scholarly journals A ”Clickable” Probe for Active MGMT in Glioblastoma Demonstrates Two Discrete Populations of MGMT

Cancers ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 453 ◽  
Author(s):  
Sudhir Raghavan ◽  
David S. Baskin ◽  
Martyn A. Sharpe
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Cancer Cells ◽  
Dna Adducts ◽  
Alkylating Agents ◽  
Chemotherapeutic Agents ◽  
Dna Alkylation ◽  
Methylated Dna ◽  
Methylguanine Methyltransferase ◽  
Discrete Populations

Various pathways can repair DNA alkylation by chemotherapeutic agents such as temozolomide (TMZ). The enzyme O6-methylguanine methyltransferase (MGMT) removes O6-methylated DNA adducts, leading to the failure of chemotherapy in resistant glioblastomas. Because of the anti-chemotherapeutic activities of MGMT previously described, estimating the levels of active MGMT in cancer cells can be a significant predictor of response to alkylating agents. Current methods to detect MGMT in cells are indirect, complicated, time-intensive, or utilize molecules that require complex and multistep chemistry synthesis. Our design simulates DNA repair by the transfer of a clickable propargyl group from O6-propargyl guanine to active MGMT and subsequent attachment of fluorescein-linked PEG linker via ”click chemistry.” Visualization of active MGMT levels reveals discrete active and inactive MGMT populations with biphasic kinetics for MGMT inactivation in response to TMZ-induced DNA damage.

scholarly journals Kinase-dead ATM protein is highly oncogenic and can be preferentially targeted by Topo-isomerase I inhibitors

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Kenta Yamamoto ◽  
Jiguang Wang ◽  
Lisa Sprinzen ◽  
Jun Xu ◽  
Christopher J Haddock ◽  
...  
Keyword(s):  
Dna Damage ◽  
Cancer Therapy ◽  
Animal Models ◽  
Dna Adducts ◽  
Kinase Domain ◽  
Missense Mutations ◽  
Atm Kinase ◽  
Dna Damage Responses ◽  
Atm Protein ◽  
Kinase A

Missense mutations in ATM kinase, a master regulator of DNA damage responses, are found in many cancers, but their impact on ATM function and implications for cancer therapy are largely unknown. Here we report that 72% of cancer-associated ATM mutations are missense mutations that are enriched around the kinase domain. Expression of kinase-dead ATM (AtmKD/-) is more oncogenic than loss of ATM (Atm-/-) in mouse models, leading to earlier and more frequent lymphomas with Pten deletions. Kinase-dead ATM protein (Atm-KD), but not loss of ATM (Atm-null), prevents replication-dependent removal of Topo-isomerase I-DNA adducts at the step of strand cleavage, leading to severe genomic instability and hypersensitivity to Topo-isomerase I inhibitors. Correspondingly, Topo-isomerase I inhibitors effectively and preferentially eliminate AtmKD/-, but not Atm-proficientor Atm-/- leukemia in animal models. These findings identify ATM kinase-domain missense mutations as a potent oncogenic event and a biomarker for Topo-isomerase I inhibitor based therapy.

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