Quartz Exposure of the Rat Lung Leads to a Linear Dose Response in Inflammation but Not in Oxidative DNA Damage and Mutagenicity

2001 ◽  
Vol 24 (4) ◽  
pp. 492-498 ◽  
Author(s):  
Frank Seiler ◽  
Bernd Rehn ◽  
S. Rehn ◽  
Martina Hermann ◽  
Joachim Bruch
Keyword(s):  
Dna Damage ◽  
Dose Response ◽  
Oxidative Dna Damage ◽  
Rat Lung ◽  
Linear Dose

scholarly journals Genotoxicity and Gene Expression in the Rat Lung Tissue following Instillation and Inhalation of Different Variants of Amorphous Silica Nanomaterials (aSiO2 NM)

Nanomaterials ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 1502
Author(s):  
Fátima Brandão ◽  
Carla Costa ◽  
Maria João Bessa ◽  
Elise Dumortier ◽  
Florence Debacq-Chainiaux ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Damage ◽  
Amorphous Silica ◽  
Oxidative Dna Damage ◽  
Intratracheal Instillation ◽  
Dna Lesions ◽  
Lung Cells ◽  
Rat Lung ◽  
Inhalation Study

Several reports on amorphous silica nanomaterial (aSiO2 NM) toxicity have been questioning their safety. Herein, we investigated the in vivo pulmonary toxicity of four variants of aSiO2 NM: SiO2_15_Unmod, SiO2_15_Amino, SiO2_7 and SiO2_40. We focused on alterations in lung DNA and protein integrity, and gene expression following single intratracheal instillation in rats. Additionally, a short-term inhalation study (STIS) was carried out for SiO2_7, using TiO2_NM105 as a benchmark NM. In the instillation study, a significant but slight increase in oxidative DNA damage in rats exposed to the highest instilled dose (0.36 mg/rat) of SiO2_15_Amino was observed in the recovery (R) group. Exposure to SiO2_7 or SiO2_40 markedly increased oxidative DNA lesions in rat lung cells of the exposure (E) group at every tested dose. This damage seems to be repaired, since no changes compared to controls were observed in the R groups. In STIS, a significant increase in DNA strand breaks of the lung cells exposed to 0.5 mg/m3 of SiO2_7 or 50 mg/m3 of TiO2_NM105 was observed in both groups. The detected gene expression changes suggest that oxidative stress and/or inflammation pathways are likely implicated in the induction of (oxidative) DNA damage. Overall, all tested aSiO2 NM were not associated with marked in vivo toxicity following instillation or STIS. The genotoxicity findings for SiO2_7 from instillation and STIS are concordant; however, changes in STIS animals were more permanent/difficult to revert.

scholarly journals Oxidative DNA damage in the rat lung induced by intratracheal instillation and inhalation of nanoparticles

2018 ◽  
Vol 62 (3) ◽  
pp. 238-241 ◽  
Author(s):  
Yun-Shan Li ◽  
Yuko Ootsuyama ◽  
Yuya Kawasaki ◽  
Yasuo Morimoto ◽  
Toshiaki Higashi ◽  
...  
Keyword(s):  
Dna Damage ◽  
Oxidative Dna Damage ◽  
Intratracheal Instillation ◽  
Rat Lung

scholarly journals Direct and Oxidative DNA Damage in a Group of Painters Exposed to VOCs: Dose – Response Relationship

2020 ◽  
Vol 8 ◽  
Author(s):  
Renata Sisto ◽  
Delia Cavallo ◽  
Cinzia Lucia Ursini ◽  
Anna Maria Fresegna ◽  
Aureliano Ciervo ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dose Response ◽  
Oxidative Dna Damage ◽  
Response Relationship ◽  
Dose Response Relationship

scholarly journals The bile acid deoxycholic acid has a non-linear dose response for DNA damage and possibly NF- B activation in oesophageal cells, with a mechanism of action involving ROS

Mutagenesis ◽  
2008 ◽  
Vol 23 (5) ◽  
pp. 399-405 ◽  
Author(s):  
G. J. S. Jenkins ◽  
J. Cronin ◽  
A. Alhamdani ◽  
N. Rawat ◽  
F. D'Souza ◽  
...  
Keyword(s):  
Dna Damage ◽  
Bile Acid ◽  
Mechanism Of Action ◽  
Dose Response ◽  
Deoxycholic Acid ◽  
Linear Dose ◽  
Non Linear

scholarly journals Are There Thresholds in Glioblastoma Cell Death Responses Triggered by Temozolomide?

2019 ◽  
Vol 20 (7) ◽  
pp. 1562 ◽  
Author(s):  
Yang He ◽  
Bernd Kaina
Keyword(s):  
Dna Damage ◽  
Dose Response ◽  
P53 Protein ◽  
Dose Range ◽  
Dependent Manner ◽  
Response Curves ◽  
Damage Level ◽  
Therapeutic Implications ◽  
Linear Dose ◽  
Different Doses

Temozolomide (TMZ) is an alkylating agent used in the treatment of high-grade malignant glioma, notably glioblastoma multiforme, the most aggressive form of brain cancer. The drug induces a dozen DNA methylation adducts, including O6-methylguanine (O6MeG), which is the most toxic primary DNA lesion as it causes the formation of DNA double-strand breaks (DSBs) that trigger apoptosis. In p53 wild-type cells, TMZ activates p-p53ser15 and p-p53ser46, which have opposing dual functions regulating survival and death, respectively. Since the use of TMZ in a therapeutic setting is limited because of its side effects, the question arises as to the existence of threshold doses that activate the death pathway and start apoptosis. To determine whether there is a threshold for the TMZ-induced DNA damage response and exploring the factors regulating the switch between p53 dependent survival and death, the glioblastoma lines LN-229 (deficient in MGMT) and LN-229MGMT (stably transfected with MGMT) were exposed to different doses of TMZ. p53 protein expression and phosphorylation levels of p-p53ser15 and p-p53ser46 were determined by Western blotting. Also, apoptosis, senescence and autophagy levels were checked after different doses of TMZ. The results show that pro-survival p-p53ser15 and pro-death p-p53ser46 were induced by O6MeG in a specific dose- and time-dependent manner. p-p53ser15 was an early response while p-p53ser46 was activated at later times following treatment. Unexpectedly, the dose-response curves for total p53, p-p53ser15 and p-p53ser46 were linear, without an obvious threshold. O6MeG induces apoptosis late after treatment as a linear function of TMZ dose. This was observed for both p53 proficient LN-229 and p53 lacking LN-308 cells. A linear dose-response after TMZ was also observed for senescence and autophagy as well as γH2AX, an indicator of DSBs that are considered to be the downstream trigger of apoptosis, senescence and autophagy. LN-229MGMT cells were highly resistant to all measured endpoints because of repair of the critical primary lesion. Although LN-308 were less responsive than LN-229 to TMZ, they displayed the same TMZ-induced DSB level. The observed linear dose-responses are not compatible with the view that low DNA damage level evokes survival while high damage level activates death functions. The data bear important therapeutic implications as they indicate that even low doses of TMZ may elicit a cytotoxic response. However, since O6MeG triggers apoptosis, senescence and autophagy in the same dose range, it is likely that the accumulation of senescent cells in the population counteracts the killing effect of the anticancer drug.

Acrylamide Exposure and Oxidative DNA Damage, Lipid Peroxidation and Fasting Plasma Glucose Alteration: Association and Mediation Analyses in Chinese Urban Adults

2020 ◽  
Author(s):  
Bin Wang ◽  
Weihong Qiu ◽  
Shijie Yang ◽  
Limin Cao ◽  
Chunmei Zhu ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Dna Damage ◽  
Plasma Glucose ◽  
Fasting Plasma Glucose ◽  
Oxidative Dna Damage ◽  
Adult Population ◽  
Prostaglandin F2α ◽  
Mediation Analyses ◽  
Mediating Role ◽  
Fasting Plasma

<a><b>OBJECTIVE: </b></a>Acrylamide exposure from daily-consumed food has raised global concern.<b> </b>We aimed to assess the exposure-response relationships of internal acrylamide exposure with oxidative DNA damage, lipid peroxidation and fasting plasma glucose (FPG) alteration, and investigate the mediating role of oxidative DNA damage and lipid peroxidation in the association of internal acrylamide exposure with FPG. <p><b>RESEARCH DESIGN AND METHODS:</b> FPG and urinary biomarkers of oxidative DNA damage (8-hydroxy-deoxy-guanosine, 8-OHdG), lipid peroxidation (8-iso-prostaglandin-F2α, 8-iso-PGF2α) and acrylamide exposure (N-acetyl-S-(2-carbamoylethyl)-L-cysteine, AAMA; N-acetyl-S-(2-carbamoyl-2-hydroxyethyl)-L-cysteine, GAMA) were measured for 3,270 general adults from the Wuhan-Zhuhai cohort. The associations of urinary acrylamide metabolites with 8-OHdG, 8-iso-PGF2α and FPG were assessed by linear mixed models. The mediating roles of 8-OHdG and 8-iso-PGF2α were evaluated by mediation analysis.</p> <p><b>RESULTS:</b> We found significant linear positive dose-response relationships of urinary acrylamide metabolites with 8-OHdG, 8-iso-PGF2α and FPG (except GAMA with FPG), and 8-iso-PGF2α with FPG. Each 1-unit increase in log-transformed level of AAMA, ΣUAAM (AAMA+GAMA) or 8-iso-PGF2α was associated with a 0.17-, 0.15- or 0.23-mmol/L increase in FPG, respectively (<i>P </i>or/and<i> P trend</i><0.05). Each 1% increase in AAMA, GAMA or ΣUAAM was associated with a 0.19%, 0.27% or 0.22% increase in 8-OHdG, respectively, and a 0.40%, 0.48% or 0.44% increase in 8-iso-PGF2α, respectively (<i>P </i>and<i> P trend</i><0.05). Increased 8-iso-PGF2α rather than 8-OHdG significantly mediated 64.29% and 76.92% of the AAMA and ΣUAAM associated-FPG increases, respectively.</p> <p><b>CONCLUSIONS:</b> Exposure of general adult population to acrylamide was associated with FPG elevation, oxidative DNA damage and lipid peroxidation, which in turn partly mediated acrylamide-associated FPG elevation.<b></b></p>

Serum of 8-OHdG as a potential biomarker of oxidative DNA damage in workers exposed to harmful working environments

2020 ◽  
pp. 783-783
Author(s):  
I. A. Umnyagina ◽  
L. A. Strakhova ◽  
T. V. Blinova
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Blood Serum ◽  
Oxidative Dna Damage ◽  
Working Environment ◽  
Working Environments ◽  
Potential Biomarker ◽  
High Level ◽  
Damage Marker

In the blood serum of 70% individuals exposed to harmful factors of the working environment, a high level of oxidative stress and the DNA damage marker 8-Hydroxy-2’-Deoxyguanosine (8-OHdG) were detected.

Sign in / Sign up

Export Citation Format

Share Document