Analysis of mutant frequencies and mutation spectra in hMTH1 knockdown TK6 cells exposed to UV radiation

Fotouhi, Asal; Hagos, Winta Woldai; Ilić, Marko; Wójcik, Andrzej; Harms‐Ringdahl, Mats; Gruijl, Frank de; Mullenders, Leon H.F.; Jansen, Jacob G.; Haghdoost, Siamak

doi:10.1016/j.mrfmmm.2013.10.001

Cited by 9 publications

(9 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Modified dNTPs can be incorporated into the DNA during replication, causing point mutations [7]. One of the most studied modifications of dNTP is 8-hydroxy-2′-deoxyguanosine-triphosphate (8-oxo-dGTP), which is formed when ROS react with deoxyguanosine triphosphate (dGTP).…”

Section: Introductionmentioning

confidence: 99%

Possible benefits of tomato juice consumption: a pilot study on irradiated human lymphocytes from healthy donors

Nakamura

Itaki

Saito

et al. 2017

Nutr J

Self Cite

View full text Add to dashboard Cite

BackgroundReactive oxygen species (ROS) mediate much of the DNA damage caused by ionizing radiation. Among carotenoids, lycopene and β-carotene, present in tomato juice, are known to be strong radical scavengers. The aim of the study was to investigate the effect of tomato juice intake on the levels of DNA damage and oxidative stress in human whole blood induced by in vitro exposure to X-rays.MethodsTen healthy adults were asked to drink 190 g of tomato juice, containing 17 mg lycopene and 0.25 mg β-carotene, per day for 3 weeks and then refrain from drinking it for 3 weeks. Peripheral whole blood samples were collected before and after the intake period of tomato juice and after the washout period. The blood samples were exposed in vitro to X-ray doses of 0, 0.1, 0.5, and 2 Gy. Cytogenetic damage was measured using the cytokinesis-block micronucleus (CBMN) assay and the dicentrics (DIC) assay. The level of oxidative stress was determined using serum 8-oxo-7, 8-dihydro-2-deoxyguanosine (8-oxo-dG) and plasma reactive oxygen metabolite-derived compounds (d-ROMs). The concentration of carotenoids in plasma was measured at the three time points.ResultsThe levels of 8-oxo-dG tended to decrease during the intake period and increase during the washout period. A non-significant inverse correlation was noted between the plasma concentration of lycopene plus β-carotene and the level of 8-oxo-dG (P = 0.064). The radiation-induced MN and DIC frequencies increased in a dose-dependent manner, and when compared at the same dose, the MN and DIC frequencies decreased during the intake period compared with those at baseline and then increased during the washout period. The results suggest that continuous tomato juice consumption non-significantly decreases extracellular 8-oxo-dG, d-ROMs, and MN. Tomato juice intake had minimal or no effect on radiation-induced 8-oxo-dG and d-ROMs. For most radiation doses, continuously tomato juice intake lowered the levels of MN and DIC.ConclusionTomato juice consumption may suppress human lymphocyte DNA damage caused by radiation, but further examination is required.Trial registration 2014-001 and 2014-R06.

show abstract

Section: Introductionmentioning

confidence: 99%

Possible benefits of tomato juice consumption: a pilot study on irradiated human lymphocytes from healthy donors

Nakamura

Itaki

Saito

et al. 2017

Nutr J

Self Cite

View full text Add to dashboard Cite

show abstract

“…ROS react with dGTP and lead to the production of 8-oxo-dGTP in the cytoplasm [15,20]. MutT homolog (MTH1) converts 8-oxo-dGTP into 8-oxo-dGMP [44,45] to inhibit its incorporation into the DNA during DNA replication and repair [44]. 8-Oxo-dGMP is then converted to 8-oxo-dG by unknown enzyme(s) and excreted from the intra-to the extracellular milieu and enters all biological liquids including saliva.…”

Section: Discussionmentioning

confidence: 99%

“…8-Oxo-dGMP is then converted to 8-oxo-dG by unknown enzyme(s) and excreted from the intra-to the extracellular milieu and enters all biological liquids including saliva. This mechanism has been in focus within our research group [15,20,[45][46][47]. During the intervention after extensive physical activity, antioxidant content of tomato juice may react with ROS and keep their concentration low leading to lower production of 8-oxo-dGTP.…”

Section: Discussionmentioning

confidence: 99%

Effects of Tomato Juice Intake on Salivary 8-Oxo-dG Levels as Oxidative Stress Biomarker after Extensive Physical Exercise

Khavari

Haghdoost

2020

Oxidative Medicine and Cellular Longevity

Self Cite

View full text Add to dashboard Cite

Reactive oxygen species (ROS) at a normal level are important molecules involved in several cellular processes including immune response and cell signalling. Overproduction of ROS may lead to elevated oxidative stress and consequently to age-related diseases. Most of the studies related to oxidative stress in humans have been done on blood samples. However, blood sampling might be painful, requires special qualified personnel, and has to be performed at medical centers. An alternative to blood is saliva. Saliva sampling is noninvasive and can be performed by the donor. Biomarker determination in saliva is becoming an important part of laboratory diagnosis, but method development is needed before it can be used in the clinics. In the present investigation, 16 donors performed extensive physical exercise by cycling and keeping their heart rate at 80% of maximum for 20 minutes. The physical activity was repeated 3 times: before tomato juice intake, after daily intake of 100 ml tomato juice during 3 weeks, and finally 3 weeks after finishing tomato juice intake (washout period). The level of the stress biomarker, salivary 8-oxo-dG, was determined before and after the physical activity. The results indicate that (a) 20 min extensive physical activity increases the level of 8-oxo-dG in saliva significantly (p=0.0078) and (b) daily intake of 100 ml tomato juice may inhibit (p=0.052) overproduction of salivary 8-oxo-dG by 20 min physical activity. We conclude that the 20 min extensive physical activity increases the level of salivary 8-oxo-dG in healthy donors and 100 ml daily intake of tomato juice may inhibit the increase of 8-oxo-dG in saliva.

show abstract

“…We observed a transient and moderate reduction in the intracellular levels of dATP, dCTP and dTTP ( Fig 4 ), and a transient oxidation of RRM1 subunit of RNR ( Fig 5 ). It is well known that UVA-induced ROS is expected to partly oxidize dNTPs, especially dATP to 2-OH-dATP and dGTP to 8oxo-dGTP [ 74 , 75 ]. However, the dGTP pool was not modified ( Fig 4 ) suggesting that the moderate drop of dATP, dCTP and dTTP is not due to their oxidation.…”

Section: Discussionmentioning

confidence: 99%

Singlet Oxygen-Mediated Oxidation during UVA Radiation Alters the Dynamic of Genomic DNA Replication

et al. 2015

View full text Add to dashboard Cite

UVA radiation (320–400 nm) is a major environmental agent that can exert its deleterious action on living organisms through absorption of the UVA photons by endogenous or exogenous photosensitizers. This leads to the production of reactive oxygen species (ROS), such as singlet oxygen (1O2) and hydrogen peroxide (H2O2), which in turn can modify reversibly or irreversibly biomolecules, such as lipids, proteins and nucleic acids. We have previously reported that UVA-induced ROS strongly inhibit DNA replication in a dose-dependent manner, but independently of the cell cycle checkpoints activation. Here, we report that the production of 1O2 by UVA radiation leads to a transient inhibition of replication fork velocity, a transient decrease in the dNTP pool, a quickly reversible GSH-dependent oxidation of the RRM1 subunit of ribonucleotide reductase and sustained inhibition of origin firing. The time of recovery post irradiation for each of these events can last from few minutes (reduction of oxidized RRM1) to several hours (replication fork velocity and origin firing). The quenching of 1O2 by sodium azide prevents the delay of DNA replication, the decrease in the dNTP pool and the oxidation of RRM1, while inhibition of Chk1 does not prevent the inhibition of origin firing. Although the molecular mechanism remains elusive, our data demonstrate that the dynamic of replication is altered by UVA photosensitization of vitamins via the production of singlet oxygen.

show abstract

Analysis of mutant frequencies and mutation spectra in hMTH1 knockdown TK6 cells exposed to UV radiation

Cited by 9 publications

References 21 publications

Possible benefits of tomato juice consumption: a pilot study on irradiated human lymphocytes from healthy donors

Possible benefits of tomato juice consumption: a pilot study on irradiated human lymphocytes from healthy donors

Effects of Tomato Juice Intake on Salivary 8-Oxo-dG Levels as Oxidative Stress Biomarker after Extensive Physical Exercise

Singlet Oxygen-Mediated Oxidation during UVA Radiation Alters the Dynamic of Genomic DNA Replication

Contact Info

Product

Resources

About