scholarly journals Genetic Polymorphisms and Pesticide-Induced DNA Damage: A Review

2021 ◽  
Vol 15 (1) ◽  
pp. 119-130
Author(s):  
Muhammad Bello Usman ◽  
Kanu Priya ◽  
Soumya Pandit ◽  
Piyush Kumar Gupta ◽  
Sharad Agrawal ◽  
...  
Keyword(s):  
Dna Damage ◽  
Genetic Polymorphisms ◽  
Cancer Biology ◽  
Metabolizing Enzymes ◽  
Pesticide Toxicity ◽  
Adverse Health Effects ◽  
Polymorphic Genes ◽  
Drastic Increase ◽  
Recent Developments ◽  
Glutathione S Transferases

The drastic increase in pesticide applications makes human exposure inevitable either through environment or occupation. Pesticide toxicity causes many adverse health effects through a number of pathways leading to DNA damage, mutations and cancers. Nevertheless, there is heterogeneity in the degree of toxicity among individuals due to the influence of genetic polymorphisms on xenobiotic metabolizing enzymes (XMEs) that modulate the biological process. Thus, study of the most common polymorphic genes coding for the enzymes involved in pesticide metabolism (such as cytochrome P450, Glutathione S-transferases, N-acetyltransferase and paraoxonase) may help determine individual’s susceptibility to pesticide toxicity. In this review, we give an overview of some recent developments in the field of genetic polymorphism and pesticide-related DNA damage, including probable biomarkers that may uncover genome susceptibility to pesticide toxicity. We have tried to create a connection between DNA polymorphism and cancer onslaught globally. It is envisaged that knowledge on this line would improve our understanding of facilitating the association between genotype and phenotype in cancer biology.

Modification of the relationship between urinary 8-OHdG and hippuric acid concentration by GSTM1, GSTT1, and ALDH2 genotypes

2010 ◽  
Vol 30 (4) ◽  
pp. 338-342 ◽  
Author(s):  
Yong-Dae Kim ◽  
Sang-Yong Eom ◽  
Yan Wei Zhang ◽  
Hyeongsu Kim ◽  
Jung-Duk Park ◽  
...  
Keyword(s):  
Dna Damage ◽  
Occupational Exposure ◽  
Genetic Polymorphisms ◽  
Hippuric Acid ◽  
Oxidative Dna Damage ◽  
Statistical Significance ◽  
Biological Marker ◽  
Metabolizing Enzymes ◽  
Toluene Exposure ◽  
The Relationship

Urinary hippuric acid (HA) has been widely used as a biological marker of occupational exposure to toluene, although it is no longer valid for low levels of toluene exposure. Toluene exposure is known to induce oxidative DNA damage and the metabolism is affected by genetic polymorphisms of some metabolizing enzymes. Therefore, genetic polymorphisms of these metabolizing enzymes must be considered in the evaluation of oxidative stress caused by toluene exposure. We evaluated the relationship between urinary 8-hydroxydeoxyguanosine (8-OHdG), a marker of oxidative DNA damage, and urinary HA in individuals without occupational exposure to toluene and characterized the possible roles of GSTM1, GSTT1, and aldehyde dehydrogenase 2 (ALDH2) genotypes in the relationships between these markers. In this study, we enrolled 92 healthy Koreans. Urinary HA and 8-OHdG levels were measured and the correlations between them were statistically tested according to the GSTM1, GSTT1, and ALDH2 genotypes. HA did not significantly correlate with urinary 8-OHdG in overall subjects. However, the correlation between them showed a statistical significance in individuals with GSTM1-null, GSTT1-null, and ALDH2 *2/*2 genotypes (r = 0.766, p < 0.01). This study shows that the relationship between urinary HA and 8-OHdG concentration is modified by genetic polymorphisms of some metabolizing enzymes such as GSTM1, GSTT1, and ALDH2.

scholarly journals O2: TOWARDS A LIVING BIOBANK OF SURGICALLY-RELEVANT 3-DIMENSIONAL GLIOBLASTOMA STEM CELL MODELS TO EVALUATE NOVEL THERAPEUTICS AND INTERROGATE INTRATUMOURAL HETEROGENEITY

2021 ◽  
Vol 108 (Supplement_1) ◽  
Author(s):  
O Rominiyi ◽  
A Vanderlinden ◽  
K Myers ◽  
N Gomez-Roman ◽  
D Dar ◽  
...  
Keyword(s):  
Dna Damage ◽  
Stem Cell ◽  
Cancer Biology ◽  
Residual Disease ◽  
Dna Damage Repair ◽  
Stem Cell Marker ◽  
Left Behind ◽  
Glioblastoma Stem Cell ◽  
Damage Repair ◽  
Intratumoural Heterogeneity

Abstract Introduction Glioblastoma is the most common cancer arising within the brain. Despite surgery, followed by DNA-damaging chemoradiotherapy, average survival remains between 12-15 months. Unacceptable survival rates underline the need to develop preclinical research models which recapitulate features underpinning therapeutic resistance in patients, such as intratumoural heterogeneity and treatment resistant glioblastoma stem cell (GSC) subpopulations which demonstrate elevated DNA damage response (DDR) activity. Method Tumour specimens from patients were used to generate 2D and 3D scaffold-based GSC models, with a range of preclinical survival and molecular assays used to interrogate cancer biology and assess therapeutic responses. Result We have developed a ‘living biobank’ of 20+ ex-vivo GSC models which reflect key clinicopathological diversity. These models include residual disease models based on careful macrodissection of rare en-blocpartial lobectomy specimens to liberate parallel GSC lines from the tumour core and adjacent infiltrated brain, to represent cells typically left behind after surgery. Therapeutic strategies targeting fundamental DDR processes demonstrate preclinical efficacy, for example dual inhibition of ATR and the FA DNA damage repair pathways elicits profound radiosensitisation (sensitiser enhancement ratio of 3.23 (3.03-3.49, 95%-CI)) with evidence of delayed DNA damage repair on single-cell gel electrophoresis. Finally, characterisation of our surgically-relevant resected and residual models reveals numerous divergent properties including elevated stem cell marker expression in residual models (p=0.0021), which may partially explain treatment resistance in disease left behind after surgery. Conclusion Our living biobank represents a useful resource for preclinical glioblastoma research and demonstrates the value of partnership between surgeons and laboratory-based scientists. Take-home message Our living biobank represents a useful resource for preclinical glioblastoma research and demonstrates the value of partnership between surgeons and laboratory-based scientists.

scholarly journals The DNA damage inducible lncRNA SCAT7 regulates genomic integrity and topoisomerase 1 turnover in lung adenocarcinoma

NAR Cancer ◽  
2021 ◽  
Vol 3 (1) ◽  
Author(s):  
Luisa Statello ◽  
Mohamad M Ali ◽  
Silke Reischl ◽  
Sagar Mahale ◽  
Subazini Thankaswamy Kosalai ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Damage Response ◽  
Cancer Biology ◽  
Topoisomerase I ◽  
Cell Cycle Checkpoints ◽  
Topoisomerase 1 ◽  
Damage Response ◽  
Promote Cell Survival

Abstract Despite the rapid improvements in unveiling the importance of lncRNAs in all aspects of cancer biology, there is still a void in mechanistic understanding of their role in the DNA damage response. Here we explored the potential role of the oncogenic lncRNA SCAT7 (ELF3-AS1) in the maintenance of genome integrity. We show that SCAT7 is upregulated in response to DNA-damaging drugs like cisplatin and camptothecin, where SCAT7 expression is required to promote cell survival. SCAT7 silencing leads to decreased proliferation of cisplatin-resistant cells in vitro and in vivo through interfering with cell cycle checkpoints and DNA repair molecular pathways. SCAT7 regulates ATR signaling, promoting homologous recombination. Importantly, SCAT7 also takes part in proteasome-mediated topoisomerase I (TOP1) degradation, and its depletion causes an accumulation of TOP1–cc structures responsible for the high levels of intrinsic DNA damage. Thus, our data demonstrate that SCAT7 is an important constituent of the DNA damage response pathway and serves as a potential therapeutic target for hard-to-treat drug resistant cancers.

Meta-analysis of contribution of genetic polymorphisms in drug-metabolizing enzymes or transporters to axitinib pharmacokinetics

2011 ◽  
Vol 68 (5) ◽  
pp. 645-655 ◽  
Author(s):  
Meghan Brennan ◽  
J. Andrew Williams ◽  
Ying Chen ◽  
Michael Tortorici ◽  
Yazdi Pithavala ◽  
...  
Keyword(s):  
Genetic Polymorphisms ◽  
Meta Analysis ◽  
Drug Metabolizing Enzymes ◽  
Metabolizing Enzymes

Genetic polymorphisms of drug-metabolizing enzymes CYP2D6, CYP2C9, CYP2C19 and CYP3A5 in the Greek population

2007 ◽  
Vol 21 (4) ◽  
pp. 419-426 ◽  
Author(s):  
Kostas Arvanitidis ◽  
Georgia Ragia ◽  
Maria Iordanidou ◽  
Sofia Kyriaki ◽  
Athanasia Xanthi ◽  
...  
Keyword(s):  
Genetic Polymorphisms ◽  
Greek Population ◽  
Drug Metabolizing Enzymes ◽  
Metabolizing Enzymes

Detection of the Nuclear Poly(ADP-ribose)-Metabolizing Enzymes and Activities in Response to DNA Damage

2008 ◽  
pp. 267-283 ◽  
Author(s):  
Jean-Christophe Amé ◽  
Antoinette Hakmé ◽  
Delphine Quenet ◽  
Elise Fouquerel ◽  
Françoise Dantzer ◽  
...  
Keyword(s):  
Dna Damage ◽  
Metabolizing Enzymes

scholarly journals Prolonged use of finasteride-induced gonadal sex steroids alterations, DNA damage and menstrual bleeding in women

2020 ◽  
Vol 40 (2) ◽  
Author(s):  
Gadah Albasher ◽  
May Bin-Jumah ◽  
Saleh Alfarraj ◽  
Fatimah Al-Otibi ◽  
Nouf K. Al-Sultan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Damage ◽  
Sex Steroids ◽  
Serum Levels ◽  
Treated Group ◽  
Heavy Menstrual Bleeding ◽  
Menstrual Bleeding ◽  
Control Group ◽  
Dna Integrity ◽  
Adverse Health Effects

Abstract The aim of the present study was to examine the effect of prolonged use of finasteride on serum levels of dihydrotestosterone (DHT), estradiol (E2), progesterone, testosterone and androstenedione in women during the menstrual period. Further, to screen and compare the 5α-reductase activities through the expression of SRD5A1, SRD5A2 and AR gene and to determine the level of VEGF, VKOR and SAA gene expression and DNA damage. A total of 30 Saudi women aged between 25 and 35 years were enrolled in the study. The selected women were divided into two groups. The first group (n = 15) received 5 mg finasteride/day for prolonged period of one year and second group (n = 15) was taken as a healthy control. ELISA technique was used for measuring the serum levels of the targeted hormones, and Comet assay was used for checking the DNA integrity. Our findings revealed significant decrement of DHT, E2, progesterone and androstenedione levels and elevated levels of testosterone in group treated with daily oral doses of 5 mg finasteride/day compared with the control subjects. mRNA expression suggested that finasteride has concrete effects on the gene expression of the selected genes from the treated group in comparison with the control group. In addition, finasteride induced DNA damage, and heavy menstrual bleeding was noted in women treated with finasteride. In conclusion, the present findings revealed that finasteride has adverse health effects in women associated with gonadal sex steroids alterations, DNA damage and heavy menstrual bleeding with no consensus in the treatment of androgenetic alopecia in women.

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