Oxidative damage of DNA in subjects occupationally exposed to lead

Pawlas, Natalia; Olewińska, Elżbieta; Markiewicz−Górka, Iwona; Kozłowska, Agnieszka; Januszewska, Lidia; Lundh, Thomas; Januszewska, Ewa; Pawlas, Krystyna

doi:10.17219/acem/64682

Cited by 39 publications

(20 citation statements)

References 22 publications

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“…During the literature review, a number of health biomonitoring studies were found that used comet assay (12)(13)(14)(15)(16). Those studies were aimed at assessing the amount of genotoxicity caused by particular exposures in the workers of different industries, such as open-cast coal mining (17), the automotive industry (18), lead battery recycling plants (19), and the petrol industry (20). A study by Megyesi et al (21) measured genotoxic DNA damage and assessed oxidative DNA damage caused by occupational exposure in groups exposed to benzene, polycyclic aromatic hydrocarbons, and styrene at the workplace so as to determine if comet assay could be used as an effective marker tool in genotoxicology (21).…”

Section: Resultsmentioning

confidence: 99%

Comet assay as a sensitive technique in occupational health studies; A literature review

Singh

2018

JOHE

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Article InfoBackground: Occupational health is a sensitive field in many countries where occupational exposure needs attention due to the lack of awareness. Several businesses, including leather, textile, iron, steel, and dyeing industries use a variety of mutagenic and genotoxic chemicals. Exposure to these chemicals may pose serious health risks, including genetic damage to workers. Comet assay is a technique that has been extensively used in assessing DNA damage in such workers. Materials and methods: The literature search was done using PubMed and Google Scholar databases. Some studies were found reporting the use of comet assay as a sensitive and useful technique in assessing genetic damage in occupationally exposed workers. These studies have been presented in this paper to emphasize the importance and propriety of comet assay in assessing the genetic impact of hazardous exposures. Result: Having gone through the available reports, the author of this paper found comet assay as a useful biotechnological technique in the field of occupational biomonitoring. This technique is a sensitive and cheap method for assessing genotoxicity. Conclusion: Comet assay can be used as a reliable technique to quantify the impact of genotoxicants in the form of DNA damage at a single-cell level. This assay can be considered as a sensitive parameter whenever health assessment studies are to be designed.

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Section: Resultsmentioning

confidence: 99%

Comet assay as a sensitive technique in occupational health studies; A literature review

Singh

2018

JOHE

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“…Oxidative stress can be provoked by lead exposure, and DNA damage is an important consequence of oxidative stress. It has been reported that 8‐hydroxydeoxyguanosine (8‐OhdG), a molecular marker for DNA oxidative damage was significantly increased in the urine of occupationally manifested individuals (Pawlas et al, ). A recent study by Lui et al () demonstrated that Pb produced genotoxic effects through increased oxidative damage and reduced the expression of genes involved in DNA repair by promotor methylation in human lymphoblastoid TK6 cell.…”

Section: Discussionmentioning

confidence: 99%

“…Oxidative stress can be provoked by lead exposure, and DNA damage is an important consequence of oxidative stress. It has been reported that 8-hydroxydeoxyguanosine (8-OhdG), a molecular marker for DNA oxidative damage was significantly increased in the urine of occupationally manifested individuals (Pawlas et al, 2017).…”

Section: Demonstrated That Lead Acetatementioning

confidence: 99%

Antigenotoxic effects of morin against lead induced genomic damage in cultured human peripheral blood lymphocytes

et al. 2019

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Lead (Pb) is a well‐known carcinogenic heavy metal. Exposure to Pb induces DNA damage by enhancing the generation of reactive oxygen species (ROS). One of the possible ways to shield DNA from this damage is to supply antioxidants that can remove free radicals generated by genotoxicants. Hence, the current study was designed to evaluate the antigenotoxic potential of a flavonoid compound; morin against Pb‐induced genomic damage on cultured human peripheral blood lymphocytes (PBL). The effect of Pb or morin or their combination was evaluated on the DNA damage using comet and sister chromatid exchange (SCE) assays. The results indicated a significant (p < 0.05) increase in the SCE frequency and various comet parameters in a dose‐dependent manner upon treatment with lead as compared to control in cultured PBL. Supplementation of morin along with Pb effectively negated DNA damage as measured by SCE frequency and comet parameters. Practical applications Results of our current study suggest that the DNA damage induced by genotoxicants can be overcome by co‐treatment with natural antioxidants, found in dietary supplements such as vegetables and fruits.

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“…To further test the clinical relevance of these in vitro findings, we collected urine samples obtained in a previously conducted clinical pharmacokinetic study of HIV/TB patients, 19 to test for 8-OhDG concentrations, a stable marker of oxidative DNA damage, which has been linked to exposures to toxins such as cadmium 25 , chromium, and lead 26 in other patient cohorts. Demographic, clinical, and immunologic characteristics of study participants are shown in Table 2, which shows that none of the characteristics differed NAT2 genotype.…”

Section: Oxidative Dna Damage Among Isoniazid-treated Tb Patientsmentioning

confidence: 99%

Redox imbalance and oxidative DNA damage during isoniazid treatment: A clinical and translational pharmacokinetic study

Zentner¹,

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Kagan

et al. 2020

Preprint

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Background: The potential for hepatotoxicity during isoniazid-based tuberculosis (TB) treatment presents a major challenge for TB control programs worldwide. We sought to determine whether pharmacokinetic exposures of isoniazid and its metabolites were related to cellular oxidation/reduction status and downstream markers of oxidative DNA damage. Methods: We performed intensive pharmacokinetic sampling among isoniazid-treated patients to determine the relative plasma exposures of isoniazid, acetylisoniazid, hydrazine, and acetylhydrazine. Physiologically-based pharmacokinetic modeling was used to estimate liver tissue exposures during a 24-hour dosing interval for each compound. We experimentally treated HepG2 cells with isoniazid and metabolites at equimolar concentrations corresponding to these exposures for 7, 14, and 28 day periods, and performed assays related to redox imbalance and oxidative DNA damage at each timepoint. We related a urine marker of oxidative DNA damage to serum isoniazid pharmacokinetic exposures and pharmacogenetics in a clinical study. Results: Among isoniazid-treated patients, serum concentrations of hydrazine and isoniazid concentrations were highly correlated. At equimolar concentrations that approximated hepatic tissue exposures during a 24-hour dosing interval, hydrazine demonstrated the highest levels of redox imbalance, mitochondrial injury, and oxidative DNA damage over a 28-day treatment period. In a clinical validation study of isoniazid-treated TB patients, peak isoniazid serum concentrations were positively associated with a urine biomarker of oxidative DNA damage. Conclusions: Isoniazid and its metabolites share the potential for oxidative cellular damage, with the greatest effects observed for hydrazine. Future studies should investigate the clinical consequences of oxidative stress with regards to clinical episodes of drug induced liver injury during isoniazid treatment.

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Oxidative damage of DNA in subjects occupationally exposed to lead

Abstract: Background. Exposure to lead (Pb) in environmental and occupational settings continues to be a serious public health problem and may pose an elevated risk of genetic damage.

Cited by 39 publications

References 22 publications

Comet assay as a sensitive technique in occupational health studies; A literature review

Comet assay as a sensitive technique in occupational health studies; A literature review

Antigenotoxic effects of morin against lead induced genomic damage in cultured human peripheral blood lymphocytes

Redox imbalance and oxidative DNA damage during isoniazid treatment: A clinical and translational pharmacokinetic study

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