Biological indicators of genotoxic risk and metabolic polymorphisms

Pavanello, Sofia; Clonfero, Erminio

doi:10.1016/s1383-5742(00)00051-x

Cited by 163 publications

(76 citation statements)

References 83 publications

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“…It is used to detect single-and double-stranded DNA breaks in individual cells, both in vitro and in vivo [54,55]. It is also used to quantify oxidative DNA damage, alkali-labile sites, DNA-DNA or DNA-protein cross-links and abasic sites [56][57][58]. The assay is based on the principle that the damaged DNA fragments will migrate out of the cell when an electric current is applied, whereas the undamaged DNA will remain in the cell nucleus.…”

Section: Apoptosis Assaymentioning

confidence: 99%

In vitro and in vivo toxicity assessment of nanoparticles

2017

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Nanotechnology has revolutionized gene therapy, diagnostics and environmental remediation. Their bulk production, uses and disposal have posed threat to the environment. With the appearance of these nanoparticles in the environment, their toxicity assessment is an immediate concern. This review is an attempt to summarize the major techniques used in cytotoxity determination. The review also presents a detailed and elaborative discussion on the toxicity imposed by different types of nanoparticles including carbon nanotubes, gold nanoparticles, silver nanoparticles, quantum dots, fullerenes, aluminium nanoparticles, zinc nanoparticles, iron nanoparticles, titanium nanoparticles and silica nanoparticles. It discusses the in vitro and in vivo toxological effects of nanoparticles on bacteria, microalgae, zebrafish, crustacean, fish, rat, mouse, pig, guinea pig, human cell lines and human. It also discusses toxological effects on organs such as liver, kidney, spleen, sperm, neural tissues, liver lysosomes, spleen macrophages, glioblastoma cells, hematoma cells and various mammalian cell lines. It provides information about the effects of nanoparticles on the gene-expression, growth and reproduction of the organisms.

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Section: Apoptosis Assaymentioning

confidence: 99%

In vitro and in vivo toxicity assessment of nanoparticles

2017

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“…The DNA molecule may be damaged directly by interaction with ionizing radiation or indirectly by interaction with reactive products of the degradation of water by ionizing radiation 7) . Damage to DNA is regarded as the most important initiating step in the development of cancer and genetic diseases after exposure 8) .…”

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confidence: 99%

Evaluation of DNA damage in lymphocytes of radiology personnel by comet assay

Khisroon

Khan²,

Naseem³

et al. 2015

Journal of Occupational Health

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“…Although more oxidative DNA damage was expected in GSTM1-null, GSTT1-null, and GSTP1-variant allele carriers, basal SSBs and Endo III or Fpg sites did not elevate alleles with a potential risk. As reviewed by Pavanello and Clonfero (2000), the number of studies demonstrating the positive influences of the GSTM1, GSTT1, and GSTP1 polymorphisms on comet assay parameters is limited. After Collins et al (1993) have modified the comet assay with specific endonucleases, we conducted a small-sized study to investigate the role of some polymorphic genes and oxidative DNA damage (detected with a modified comet assay) in Barrett's esophagus patients and found no association for the GSTM1 gene (Kadioglu et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

Assessment of Individual Susceptibility to Baseline DNA and Cytogenetic Damage in a Healthy Turkish Population: Evaluation with Lifestyle Factors

Kadıoğlu

Kocabaş

Demircigil

et al. 2012

Genetic Testing and Molecular Biomarkers

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Background: Cytogenetic biomarkers are most frequently used well-established endpoints in human population studies with their sensitivity for measuring exposure to genotoxic agents. They have an important role as early predictors of cancer risk. Identification of individual genotypes of metabolic gene polymorphisms helps to understand the modulation of cancer susceptibility by environmental exposures, such as cigarette smoking and other lifestyle factors. Aim: To evaluate individual susceptibility to chemicals, we determined individual DNA damage related to glutathione S-transferase (GST) genotypes (GSTM1, GSTT1, and GSTP1) in a Turkish population. Methods: Peripheral blood lymphocytes (PBL) and DNA samples of 127 subjects were analyzed for the presence of DNA damage, using single-cell gel electrophoresis (the Comet assay), and for cytogenetic parameters (chromosomal aberrations [CAs], bleomycin-induced CA, and a cytokinesis-blocked micronucleus assay), and the polymerase chain reaction/restriction fragment length polymorphism method, respectively. Results: Individuals carrying a GSTT1-null allele showed higher frequencies of CA and micronucleus (MN) ( p = 0.026, p = 0.003, respectively), whereas the GSTM1-null and GSTP1 mutant genotypes did not show any differences in cytogenetic parameters. Our findings demonstrated that none of the lifestyle factors (smoking, alcohol drinking, dietary habits, vitamin intake, and physical activity), except for vitamin intake ( p = 0.002), were significantly associated with the studied cytogenetic parameters. Conclusion: Our results suggest that the GSTT1 gene polymorphism may influence the baseline cytogenetic frequency in a healthy population. IntroductionT he role of genetic factors (early predictors) in determining human susceptibility to the carcinogenic effects of chemical agents has become a major research area in molecular epidemiology (Au, 2007). Biomarkers of early biologic effect include cytogenetic assays, such as chromosomal aberrations (CAs), micronucleus (MN), and the comet assay, which are the most frequently used endpoints in human population studies. Their sensitivity for measuring exposure to genotoxic agents and their role as early predictors of cancer risk have contributed to this success (Bonassi et al., 2005). CAs and cytokinesis-blocked micronucleus assay (CBMN) have value as biological dosimeters, and more recently, as predictors of cancer risk in epidemiological studies (Bonassi et al., 2004(Bonassi et al., , 2011. Mechanistic evidence linking CAs to early stages of cancer has been supported by the results of cohort studies that associated the CA frequency in peripheral lymphocytes of healthy individuals to future cancer incidence (Bonassi et al., 2008). Furthermore, it has been found that an increased MN frequency in peripheral blood lymphocytes predicts the risk of cancer in humans (Bonassi et al., 2007). The alkaline comet assay is also one of the most promising biomarkers to detect single-strand breaks (SSBs) as well as alkaline-labile sites under ...

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Biological indicators of genotoxic risk and metabolic polymorphisms

Cited by 163 publications

References 83 publications

In vitro and in vivo toxicity assessment of nanoparticles

In vitro and in vivo toxicity assessment of nanoparticles

Evaluation of DNA damage in lymphocytes of radiology personnel by comet assay

Assessment of Individual Susceptibility to Baseline DNA and Cytogenetic Damage in a Healthy Turkish Population: Evaluation with Lifestyle Factors

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