Different effects of DNA adducts induced by carcinogenic and noncarcinogenic azo dyes on in vitro DNA synthesis

1991 ◽  
Vol 179 (2) ◽  
pp. 817-823 ◽  
Author(s):  
Misaki Kojima ◽  
Masakuni Degawa ◽  
Yoshiyuki Hashimoto ◽  
Mariko Tada
Keyword(s):  
Dna Synthesis ◽  
Dna Adducts ◽  
Azo Dyes

scholarly journals Mechanism of DNA interstrand cross-link processing by repair nuclease FAN1

Science ◽  
2014 ◽  
Vol 346 (6213) ◽  
pp. 1127-1130 ◽  
Author(s):  
Renjing Wang ◽  
Nicole S. Persky ◽  
Barney Yoo ◽  
Ouathek Ouerfelli ◽  
Agata Smogorzewska ◽  
...  
Keyword(s):  
Dna Synthesis ◽  
Crystal Structures ◽  
Dna Adducts ◽  
Fanconi Anemia ◽  
Biochemical Data ◽  
Degenerative Diseases ◽  
Cross Link ◽  
Interstrand Cross Links ◽  
Cross Links

DNA interstrand cross-links (ICLs) are highly toxic lesions associated with cancer and degenerative diseases. ICLs can be repaired by the Fanconi anemia (FA) pathway and through FA-independent processes involving the FAN1 nuclease. In this work, FAN1-DNA crystal structures and biochemical data reveal that human FAN1 cleaves DNA successively at every third nucleotide. In vitro, this exonuclease mechanism allows FAN1 to excise an ICL from one strand through flanking incisions. DNA access requires a 5′-terminal phosphate anchor at a nick or a 1- or 2-nucleotide flap and is augmented by a 3′ flap, suggesting that FAN1 action is coupled to DNA synthesis or recombination. FAN1’s mechanism of ICL excision is well suited for processing other localized DNA adducts as well.

Formation and Persistence of Isoniazid-DNA Adducts in Mouse Tissues

1987 ◽  
Vol 6 (2) ◽  
pp. 153-158 ◽  
Author(s):  
G.B. Maru ◽  
S. Bhide ◽  
R. Saffhill ◽  
P.J. O'Connor
Keyword(s):  
Dna Synthesis ◽  
Dna Adducts ◽  
Target Tissue ◽  
Dna Templates ◽  
Modified Dna ◽  
Mouse Tissues ◽  
Tissue Differences ◽  
Neonatal Administration

Further confirmation is provided to support the identity of the product formed by the in vitro eaction of isoniazid (INH) with cytosine as 4-deamino-4-isoniazidocytosine (INH-cytosine). Use of INH-treated mice, in which the tissue DNA is prelabelled by the neonatal administration of [3H]-deoxycytidine, has revealed the presence of two other DNA products in addition to INHytosine. Tissue differences in the persistence of these three DNA products suggest the presence of repair eactions for certain adducts. These processes and the effects of hepatotoxicity lead to a selective etention of adducts in the DNA of lung which is the target tissue for INH-carcinogenicity in mice. INH-modified DNA templates are weakly promutagenic during in vitro DNA synthesis. The implications of these observations for the role of INH as an initiating agent and for the pecies differences in its carcinogenicity are discussed.

Complement (C5b-9) induces DNA synthesis in rat mesangial cells in vitro

2001 ◽  
Vol 59 (3) ◽  
pp. 905-912
Author(s):  
William G. Couser ◽  
Jeffrey W. Pippin ◽  
Stuart J. Shankland
Keyword(s):  
Dna Synthesis ◽  
Mesangial Cells

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.

Thrombopoietin-Induced Stimulation of Megakaryocyte- Enriched Bone Marrow Cultures

1979 ◽  
Author(s):  
K. L. Kellar ◽  
B. L. Evatt ◽  
C. R. McGrath ◽  
R. B. Ramsey
Keyword(s):  
Bone Marrow ◽  
Dna Synthesis ◽  
Bone Marrow Cells ◽  
Rabbit Plasma ◽  
Bone Marrow Cultures ◽  
Plasma Fractions ◽  
Marrow Cultures ◽  
Stimulation Of

Liquid cultures of bone marrow cells enriched for megakaryocytes were assayed for incorporation of 3H-thymidine (3H-TdR) into acid-precipitable cell digests to determine the effect of thrombopoietin on DNA synthesis. As previously described, thrombopoietin was prepared by ammonium sulfate fractionation of pooled plasma obtained from thrombocytopenic rabbits. A control fraction was prepared from normal rabbit plasma. The thrombopoietic activity of these fractions was determined in vivo with normal rabbits as assay animals and the rate of incorporation of 75Se-selenomethionine into newly formed platelets as an index of thrombopoietic activity of the infused material. Guinea pig megakaryocytes were purified using bovine serum albumin gradients. Bone marrow cultures containing 1.5-3.0x104 cells and 31%-71% megakaryocytes were incubated 18 h in modified Dulbecco’s MEM containing 10% of the concentrated plasma fractions from either thrombocytopenic or normal rabbits. In other control cultures, 0.9% NaCl was substituted for the plasma fractions. 3H-TdR incorporation was measured after cells were incubated for 3 h with 1 μCi/ml. The protein fraction containing thrombopoietin-stimulating activity caused a 25%-31% increase in 3H-TdR incorporation over that in cultures which were incubated with the similar fraction from normal plasma and a 29% increase over the activity in control cultures to which 0.9% NaCl had been added. These data suggest that thrombopoietin stimulates DNA synthesis in megakaryocytes and that this tecnique may be useful in assaying thrombopoietin in vitro.

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