scholarly journals The Impact of NAT2 Acetylator Genotype on Mutagenesis and DNA Adducts from 2-Amino-9H-pyrido[2,3-b]indole

2009 ◽  
Vol 22 (4) ◽  
pp. 726-733 ◽  
Author(s):  
Robert J. Turesky ◽  
Jean Bendaly ◽  
Isil Yasa ◽  
Mark A. Doll ◽  
David W. Hein
1990 ◽  
Vol 82 (11) ◽  
pp. 927-933 ◽  
Author(s):  
F. J. van Schooten ◽  
F. E. van Leeuwen ◽  
M. J. X. Hillebrand ◽  
M. E. de Rijke ◽  
A. A. M. Hart ◽  
...  

Author(s):  
Farouk Kamel Elbaz ◽  
Hanan F Aly ◽  
Wagdy Kb Khalil ◽  
Gamila H Al ◽  
Naglaa A Hafiz ◽  
...  

ABSTRACTObjective: The aim of this study is to investigate the impact of Haematococcus pluvialis extract against oxidative stress and inflammatory cytokinesinduced by hyperglycemia in diabetic rats.Methods: Oxidative stress; lipid peroxide (as presented by Malondialdehyde; MDA) and nitric oxide (NO), beside total antioxidant capacity, enzymaticand non-enzymatic antioxidants including reduced glutathione, glutathione peroxidase, and glutathione reductase were evaluated. The inflammatorycytokines; tumor necrosis factor-alpha and interleukin-1 beta were also investigated in rats’ serum. Several analyses including expression ofantioxidant enzyme related genes, reactive oxygen species (ROS) formation and DNA adducts were performed.Results: The results showed that diabetes mellitus induced-rats exhibited increase in oxidative stress biomarkers and inflammatory cytokines, lowerexpression levels of the antioxidant enzyme genes; superoxide dismutase and glutathione S-transferase than those in control rats. In addition, diabeticrats exhibited significantly higher levels of ROS generation and 8-hydroxy-2’-deoxyguanosine (8-OHdG) formation. In contrary, supplementation ofdiabetic rats with H. pluvialis extract improved the negative effect of the hyperglycemia on antioxidant enzymes, the gene expression of antioxidantenzymes, and ROS generation as well as 8-OHdG formation.Conclusion: H. pluvialis extract decreased the oxidative stress, enhanced antioxidant status and inflammatory cytokines induced by hyperglycemiain diabetic rats. The effect of H. pluvialis extract involved in the increase of expression levels of antioxidant enzyme genes; decreased the levels of ROSgeneration and 8-OHdG formation which may be attributed to the presence of astaxanthin in H. pluvialis extract.Keywords: Haematococcus pluvialis, Hyperglycemia, Diabetes mellitus, Oxidative stress, Inflammatory cytokines, DNA adducts.


2010 ◽  
Vol 2010 ◽  
pp. 1-7 ◽  
Author(s):  
Philip S. Crooke ◽  
Fritz F. Parl

In cells, DNA repair has to keep up with DNA damage to maintain the integrity of the genome and prevent mutagenesis and carcinogenesis. While the importance of both DNA damage and repair is clear, the impact of imbalances between both processes has not been studied. In this paper, we created a combined mathematical model for the formation of DNA adducts from oxidative estrogen metabolism followed by base excision repair (BER) of these adducts. The model encompasses a set of differential equations representing the sequence of enzymatic reactions in both damage and repair pathways. By combining both pathways, we can simulate the overall process by starting from a given time-dependent concentration of 17β-estradiol (E2) and2′-deoxyguanosine, determine the extent of adduct formation and the correction by BER required to preserve the integrity of DNA. The model allows us to examine the effect of phenotypic and genotypic factors such as different concentrations of estrogen and variant enzyme haplotypes on the formation and repair of DNA adducts.


2011 ◽  
Vol 56 (2) ◽  
pp. 825-829 ◽  
Author(s):  
Hideaki Kagaya ◽  
Masatomo Miura ◽  
Takenori Niioka ◽  
Mitsuru Saito ◽  
Kazuyuki Numakura ◽  
...  

ABSTRACTThe sulfamethoxazole (SMX)-trimethoprim drug combination is routinely used as prophylaxis againstPneumocystispneumonia during the first 3 to 6 months after renal transplantation. The objective of this study was to examine the impact ofN-acetyltransferase 2 (NAT2) andCYP2C9polymorphisms on the pharmacokinetics of SMX in 118 renal transplant recipients. Starting on day 14 after renal transplantation, patients were administered 400 mg/day-80 mg/day of SMX-trimethoprim orally once daily. On day 14 after the beginning of SMX therapy, plasma SMX concentrations were determined by a high-performance liquid chromatography method. The SMX area under the concentration-time curve from 0 to 24 h (AUC0-24) for 15 recipients with theNAT2slow acetylator genotype (NAT2*5/*6, -*6/*6, -*6/*7, and -*7/*7) was significantly greater than that for 56 recipients with theNAT2rapid acetylator genotype (homozygous forNAT2*4) (766.4 ± 432.3 versus 537.2 ± 257.5 μg-h/ml, respectively;P= 0.0430), whereas there were no significant differences in the SMX AUC0-24between theCYP2C9*1/*1and -*1/*3groups. In a multiple regression analysis, the SMX AUC0-24was associated withNAT2slow acetylator polymorphisms (P= 0.0095) and with creatinine clearance (P= 0.0499). Hepatic dysfunction inNAT2slow acetylator recipient patients during the 6-month period after SMX administration was not observed. SMX plasma concentrations were affected byNAT2polymorphisms and renal dysfunction. Although standard SMX administration to patients withNAT2slow acetylator polymorphisms should be accompanied by monitoring for side effects and drug interaction effects from the inhibition of CYP2C9, SMX administration at a low dose (400 mg) as prophylaxis may not provide drug concentrations that reach the level necessary for the expression of side effects. Further studies with a larger sample size should be able to clarify the relationship between SMX plasma concentration and side effects.


1996 ◽  
Vol 93 (10) ◽  
pp. 5084-5089 ◽  
Author(s):  
N. Rothman ◽  
V. K. Bhatnagar ◽  
R. B. Hayes ◽  
T. V. Zenser ◽  
S. K. Kashyap ◽  
...  

1962 ◽  
Vol 14 ◽  
pp. 415-418
Author(s):  
K. P. Stanyukovich ◽  
V. A. Bronshten

The phenomena accompanying the impact of large meteorites on the surface of the Moon or of the Earth can be examined on the basis of the theory of explosive phenomena if we assume that, instead of an exploding meteorite moving inside the rock, we have an explosive charge (equivalent in energy), situated at a certain distance under the surface.


1962 ◽  
Vol 14 ◽  
pp. 169-257 ◽  
Author(s):  
J. Green

The term geo-sciences has been used here to include the disciplines geology, geophysics and geochemistry. However, in order to apply geophysics and geochemistry effectively one must begin with a geological model. Therefore, the science of geology should be used as the basis for lunar exploration. From an astronomical point of view, a lunar terrain heavily impacted with meteors appears the more reasonable; although from a geological standpoint, volcanism seems the more probable mechanism. A surface liberally marked with volcanic features has been advocated by such geologists as Bülow, Dana, Suess, von Wolff, Shaler, Spurr, and Kuno. In this paper, both the impact and volcanic hypotheses are considered in the application of the geo-sciences to manned lunar exploration. However, more emphasis is placed on the volcanic, or more correctly the defluidization, hypothesis to account for lunar surface features.


1997 ◽  
Vol 161 ◽  
pp. 197-201 ◽  
Author(s):  
Duncan Steel

AbstractWhilst lithopanspermia depends upon massive impacts occurring at a speed above some limit, the intact delivery of organic chemicals or other volatiles to a planet requires the impact speed to be below some other limit such that a significant fraction of that material escapes destruction. Thus the two opposite ends of the impact speed distributions are the regions of interest in the bioastronomical context, whereas much modelling work on impacts delivers, or makes use of, only the mean speed. Here the probability distributions of impact speeds upon Mars are calculated for (i) the orbital distribution of known asteroids; and (ii) the expected distribution of near-parabolic cometary orbits. It is found that cometary impacts are far more likely to eject rocks from Mars (over 99 percent of the cometary impacts are at speeds above 20 km/sec, but at most 5 percent of the asteroidal impacts); paradoxically, the objects impacting at speeds low enough to make organic/volatile survival possible (the asteroids) are those which are depleted in such species.


1997 ◽  
Vol 161 ◽  
pp. 189-195
Author(s):  
Cesare Guaita ◽  
Roberto Crippa ◽  
Federico Manzini

AbstractA large amount of CO has been detected above many SL9/Jupiter impacts. This gas was never detected before the collision. So, in our opinion, CO was released from a parent compound during the collision. We identify this compound as POM (polyoxymethylene), a formaldehyde (HCHO) polymer that, when suddenly heated, reformes monomeric HCHO. At temperatures higher than 1200°K HCHO cannot exist in molecular form and the most probable result of its decomposition is the formation of CO. At lower temperatures, HCHO can react with NH3 and/or HCN to form high UV-absorbing polymeric material. In our opinion, this kind of material has also to be taken in to account to explain the complex evolution of some SL9 impacts that we observed in CCD images taken with a blue filter.


1997 ◽  
Vol 161 ◽  
pp. 179-187
Author(s):  
Clifford N. Matthews ◽  
Rose A. Pesce-Rodriguez ◽  
Shirley A. Liebman

AbstractHydrogen cyanide polymers – heterogeneous solids ranging in color from yellow to orange to brown to black – may be among the organic macromolecules most readily formed within the Solar System. The non-volatile black crust of comet Halley, for example, as well as the extensive orangebrown streaks in the atmosphere of Jupiter, might consist largely of such polymers synthesized from HCN formed by photolysis of methane and ammonia, the color observed depending on the concentration of HCN involved. Laboratory studies of these ubiquitous compounds point to the presence of polyamidine structures synthesized directly from hydrogen cyanide. These would be converted by water to polypeptides which can be further hydrolyzed to α-amino acids. Black polymers and multimers with conjugated ladder structures derived from HCN could also be formed and might well be the source of the many nitrogen heterocycles, adenine included, observed after pyrolysis. The dark brown color arising from the impacts of comet P/Shoemaker-Levy 9 on Jupiter might therefore be mainly caused by the presence of HCN polymers, whether originally present, deposited by the impactor or synthesized directly from HCN. Spectroscopic detection of these predicted macromolecules and their hydrolytic and pyrolytic by-products would strengthen significantly the hypothesis that cyanide polymerization is a preferred pathway for prebiotic and extraterrestrial chemistry.


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