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Scientific Reports Jun 2024As patient exposure to ionizing radiation from medical imaging and its risks are continuing issues, this study aimed to evaluate DNA damage and repair markers after...
As patient exposure to ionizing radiation from medical imaging and its risks are continuing issues, this study aimed to evaluate DNA damage and repair markers after myocardial perfusion single-photon emission computed tomography (MPS). Thirty-two patients undergoing Tc-99m sestamibi MPS were studied. Peripheral blood was collected before radiotracer injection at rest and 60-90 min after injection. The comet assay (single-cell gel electrophoresis) was performed with peripheral blood cells to detect DNA strand breaks. Three descriptors were evaluated: the percentage of DNA in the comet tail, tail length, and tail moment (the product of DNA tail percentage and tail length). Quantitative PCR (qPCR) was performed to evaluate the expression of five genes related to signaling pathways in response to DNA damage and repair (ATM, ATR, BRCA1, CDKN1A, and XPC). Mann-Whitney's test was employed for statistical analysis; p < 0.05 was considered significant. Mean Tc-99m sestamibi dose was 15.1 mCi. After radiotracer injection, comparing post-exposure to pre-exposure samples of each of the 32 patients, no statistically significant differences of the DNA percentage in the tail, tail length or tail moment were found. qPCR revealed increased expression of BRCA1 and XPC, without any significant difference regarding the other genes. No significant increase in DNA strand breaks was detected after a single radiotracer injection for MPS. There was activation of only two repair genes, which may indicate that, in the current patient sample, the effects of ionizing radiation on the DNA were not large enough to trigger intense repair responses, suggesting the absence of significant DNA damage.
Topics: Humans; Female; DNA Damage; Male; Tomography, Emission-Computed, Single-Photon; DNA Repair; Middle Aged; Aged; Technetium Tc 99m Sestamibi; Myocardial Perfusion Imaging; BRCA1 Protein; Comet Assay
PubMed: 38844507
DOI: 10.1038/s41598-024-63537-3 -
Food Chemistry May 2024Laccase mediators possess advantage of oxidizing substrates with high redox potentials, such as aflatoxin B (AFB). High costs of chemically synthesized mediators limit...
Laccase mediators possess advantage of oxidizing substrates with high redox potentials, such as aflatoxin B (AFB). High costs of chemically synthesized mediators limit laccase industrial application. In this study, thin stillage extract (TSE), a byproduct of corn-based ethanol fermentation was investigated as the potential natural mediator of laccases. Ferulic acid, p-coumaric acid, and vanillic acid were identified as the predominant phenolic compounds of TSE. With the assistance of 0.05 mM TSE, AFB degradation activity of novel laccase Glac1 increased by 17 times. The promoting efficiency of TSE was similar to ferulic acid, but superior to vanillic acid and p-coumaric acid, with 1.2- and 1.3-fold increases, respectively. After Glac1-TSE treatment, two oxidation products were identified. Ames test showed AFB degradation products lost mutagenicity. Meanwhile, TSE also showed 1.3-3.0 times promoting effect on laccase degradation activity in cereal flours. Collectively, a safe and highly efficient natural mediator was obtained for aflatoxin detoxification.
PubMed: 38833866
DOI: 10.1016/j.foodchem.2024.139862 -
PloS One 2024This study aims to investigate if high-concentration HOCl fogging disinfection causes cytotoxicity and genotoxicity to cultured primary human skin fibroblasts. The cells...
This study aims to investigate if high-concentration HOCl fogging disinfection causes cytotoxicity and genotoxicity to cultured primary human skin fibroblasts. The cells were exposed to a dry fog of HOCl produced from solutions with a concentration of 300 ppm (5.72 mM) or 500 ppm (9.53 mM). After four times when fibroblasts were exposed to aerosolized HOCl at a concentration of 500 ppm for 9 minutes, significant cytotoxicity and genotoxicity effects were observed. Significant changes in the morphology of fibroblasts and cell death due to membrane disruption were observed, independent of the number of exposures. Flow cytometry analyses performed under these experimental conditions indicated a decrease in the number of cells with an intact cell membrane in the exposed samples compared to the sham samples, dropping to 49.1% of the total cells. Additionally, under the same conditions, the neutral comet assay results demonstrated significant DNA damage in the exposed cells. However, no analogous damages were found when the cells were exposed to aerosolized HOCl generated from a 300-ppm solution for 3 minutes, whether once or four times. Therefore, we have concluded that aerosolized HOCl in dry fog, with a concentration exceeding 300 ppm, can cause cytotoxic and genotoxic effects on human skin fibroblasts.
Topics: Humans; Fibroblasts; Hypochlorous Acid; DNA Damage; Cells, Cultured; Comet Assay; Skin; Aerosols; Cell Survival
PubMed: 38809935
DOI: 10.1371/journal.pone.0304602 -
Anais Da Academia Brasileira de Ciencias 2024In recent years, the use of pesticides has increased considerably for pest control and to improve agricultural production. The rural areas of several municipalities of...
In recent years, the use of pesticides has increased considerably for pest control and to improve agricultural production. The rural areas of several municipalities of department of Cordoba, north of Colombia, are highly dependent on agriculture. In this study, a questionnaire and field observations about pesticide use and genotoxic damage through the comet assay in peripheral blood lymphocytes of children who live near crop fields was evaluated. Damage Index for Comet Assay (DICA) of five children populations exposed to pesticides (mean of 94.73±53.95 for the municipality of Monteria, the higher damage in this study) were significantly Higher than control children population (mean of 7.56±7.39). Results showed the damage index in children exposed group was higher than in the control group. An inadequate management of pesticides, as well as incorrect disposal of toxic wastes was observed in the study zone.
Topics: Humans; Colombia; Child; Pesticides; Comet Assay; Male; Agriculture; Female; Environmental Exposure; DNA Damage; Rural Population; Child, Preschool; Surveys and Questionnaires; Adolescent; Lymphocytes; Case-Control Studies
PubMed: 38808810
DOI: 10.1590/0001-3765202420221111 -
Microorganisms May 2024The present study involves the precise identification and safety evaluation of KB1733, previously identified using 16S rRNA analysis, through whole-genome sequencing,...
The present study involves the precise identification and safety evaluation of KB1733, previously identified using 16S rRNA analysis, through whole-genome sequencing, phenotypic analysis, and preclinical toxicity studies. Analyses based on the genome sequencing data confirm the identity of KB1733 as and show that the genes related to vancomycin resistance are only present on the chromosome, while no virulence factor genes are present on the chromosome or plasmid. Phenotypic analyses of antibiotic resistance and hemolytic activity also indicated no safety concerns. A bacterial reverse mutation test showed there was no increase in revertant colonies of heat-killed KB1733. An acute toxicity test employing heat-killed KB1733 at a dose of 2000 mg/kg body weight in rats resulted in no deaths and no weight gain or other abnormalities in the general condition of the animals, with renal depression foci and renal cysts only occurring at the same frequency as in the control. Taking the background data into consideration, the effects on the kidneys observed in the current study were not caused by KB1733. Our findings suggest that KB1733 is non-pathogenic to humans/animals, although further studies involving repeated oral toxicity tests and/or clinical tests are required.
PubMed: 38792783
DOI: 10.3390/microorganisms12050953 -
Current Research in Toxicology 2024Nicotinamide mononucleotide (NMN) is an intermediate in biosynthesis pathway of Nicotinamide adenine dinucleotide (NAD+), an essential cofactor in all living cells...
Nicotinamide mononucleotide (NMN) is an intermediate in biosynthesis pathway of Nicotinamide adenine dinucleotide (NAD+), an essential cofactor in all living cells involved in fundamental biological processes. Evidence stemming from recent studies have unveiled numerous roles of NAD+ metabolism on aging, longevity, delaying the progression of age-related diseases. A three-study genetic toxicity (genetox) battery (bacterial mutagenesis, in vitro cytogenetics, and in vivo mammalian test) is usually required to confirm safety of a new dietary ingredient and this study showed the data from in vivo mutagenicity test for the first time. The acute oral LD50 of NMN was greater than 2000 mg/kg body weight with 5000 mg/kg body weight as LD50 cut-off value and was classified under "Category 5 or Unclassified" as per Globally Harmonized System of Classification and Labelling of Chemicals (GHS). Based on 90 days repeated dose toxicity test the NOAEL was considered to be NLT 800 mg NMN/kg body weight in Wistar rats. The bacterial reverse mutation test, the in vitro and in vivo chromosomal aberration test, found NMN to be non-mutagenic. In the mammalian bone marrow chromosomal aberration test, it was concluded that NMN is non clastogenic at and up to 2,000 mg/kg body weight in all the animals tested to confirm safety of a new dietary ingredient and this study showed the data from in vivo mutagenicity test for the first time.
PubMed: 38765763
DOI: 10.1016/j.crtox.2024.100171 -
Free Radical Biology & Medicine Aug 2024DNA damage caused by oxidative reactions plays a crucial role in the pathogenesis of colorectal cancer (CRC). In a previous cross-sectional study, CRC patients diagnosed... (Randomized Controlled Trial)
Randomized Controlled Trial
DNA damage caused by oxidative reactions plays a crucial role in the pathogenesis of colorectal cancer (CRC). In a previous cross-sectional study, CRC patients diagnosed with regional disease (stage III) exhibited a higher level of DNA base oxidation in peripheral blood mononuclear cells (PBMCs) 2-9 months post-surgery compared to those with localized disease (stage I-II). To further explore this observation over time, the present study aimed to investigate DNA base oxidation in CRC patients with localized versus regional disease 6 and 12 months after the initial measurements. The present study included patients enrolled in the randomized controlled trial Norwegian Dietary Guidelines and Colorectal Cancer Survival (CRC-NORDIET). The standard comet assay, modified with the lesion-specific enzyme formamidopyrimidine DNA glycosylase (Fpg), was applied to measure DNA base oxidation in PBMCs at the 6- and 12-month follow-ups. Of the 255 patients assessed at baseline, 156 were included at the 6-month follow-up, with 89 of these patients included in the 12-month follow-up. In contrast to our observation at baseline, there were no significant differences in the levels of DNA base oxidation between patients diagnosed with localized disease and those with regional involvement at the 6- and 12-month follow-up visits (P = 0.81 and P = 0.09, respectively). Patients with stage III disease exhibited a significant decrease in the levels of DNA base oxidation from baseline to 6 months (P < 0.01) and baseline to 12 months (P = 0.03), but no significant difference from 6 to 12 months (P = 0.80). In conclusion, the initially elevated levels of DNA base oxidation in PBMCs, observed 2-9 months post-surgery in patients diagnosed with regional disease (stage III), subsequently decreased to levels comparable to patients with localized disease (stage I-II) at the 6- and 12-month follow-ups.
Topics: Humans; Colorectal Neoplasms; Male; Female; Aged; DNA Damage; Middle Aged; Oxidation-Reduction; Leukocytes, Mononuclear; Follow-Up Studies; Neoplasm Staging; Oxidative Stress; Comet Assay; DNA-Formamidopyrimidine Glycosylase; DNA; Cross-Sectional Studies
PubMed: 38762060
DOI: 10.1016/j.freeradbiomed.2024.05.029 -
Particle and Fibre Toxicology May 2024Significant variations exist in the forms of ZnO, making it impossible to test all forms in in vivo inhalation studies. Hence, grouping and read-across is a common...
BACKGROUND
Significant variations exist in the forms of ZnO, making it impossible to test all forms in in vivo inhalation studies. Hence, grouping and read-across is a common approach under REACH to evaluate the toxicological profile of familiar substances. The objective of this paper is to investigate the potential role of dissolution, size, or coating in grouping ZnO (nano)forms for the purpose of hazard assessment. We performed a 90-day inhalation study (OECD test guideline no. (TG) 413) in rats combined with a reproduction/developmental (neuro)toxicity screening test (TG 421/424/426) with coated and uncoated ZnO nanoforms in comparison with microscale ZnO particles and soluble zinc sulfate. In addition, genotoxicity in the nasal cavity, lungs, liver, and bone marrow was examined via comet assay (TG 489) after 14-day inhalation exposure.
RESULTS
ZnO nanoparticles caused local toxicity in the respiratory tract. Systemic effects that were not related to the local irritation were not observed. There was no indication of impaired fertility, developmental toxicity, or developmental neurotoxicity. No indication for genotoxicity of any of the test substances was observed. Local effects were similar across the different ZnO test substances and were reversible after the end of the exposure.
CONCLUSION
With exception of local toxicity, this study could not confirm the occasional findings in some of the previous studies regarding the above-mentioned toxicological endpoints. The two representative ZnO nanoforms and the microscale particles showed similar local effects. The ZnO nanoforms most likely exhibit their effects by zinc ions as no particles could be detected after the end of the exposure, and exposure to rapidly soluble zinc sulfate had similar effects. Obviously, material differences between the ZnO particles do not substantially alter their toxicokinetics and toxicodynamics. The grouping of ZnO nanoforms into a set of similar nanoforms is justified by these observations.
Topics: Animals; Zinc Oxide; Male; Inhalation Exposure; Female; Metal Nanoparticles; Particle Size; Administration, Inhalation; DNA Damage; Rats; Comet Assay; Rats, Wistar; Reproduction; Lung; Liver
PubMed: 38760761
DOI: 10.1186/s12989-024-00572-y -
Regulatory Toxicology and Pharmacology... Jun 2024N-Nitrosamine impurities, including nitrosamine drug substance-related impurities (NDSRIs), have challenged pharmaceutical industry and regulators alike and affected the...
Determining recommended acceptable intake limits for N-nitrosamine impurities in pharmaceuticals: Development and application of the Carcinogenic Potency Categorization Approach (CPCA).
N-Nitrosamine impurities, including nitrosamine drug substance-related impurities (NDSRIs), have challenged pharmaceutical industry and regulators alike and affected the global drug supply over the past 5 years. Nitrosamines are a class of known carcinogens, but NDSRIs have posed additional challenges as many lack empirical data to establish acceptable intake (AI) limits. Read-across analysis from surrogates has been used to identify AI limits in some cases; however, this approach is limited by the availability of robustly-tested surrogates matching the structural features of NDSRIs, which usually contain a diverse array of functional groups. Furthermore, the absence of a surrogate has resulted in conservative AI limits in some cases, posing practical challenges for impurity control. Therefore, a new framework for determining recommended AI limits was urgently needed. Here, the Carcinogenic Potency Categorization Approach (CPCA) and its supporting scientific rationale are presented. The CPCA is a rapidly-applied structure-activity relationship-based method that assigns a nitrosamine to 1 of 5 categories, each with a corresponding AI limit, reflecting predicted carcinogenic potency. The CPCA considers the number and distribution of α-hydrogens at the N-nitroso center and other activating and deactivating structural features of a nitrosamine that affect the α-hydroxylation metabolic activation pathway of carcinogenesis. The CPCA has been adopted internationally by several drug regulatory authorities as a simplified approach and a starting point to determine recommended AI limits for nitrosamines without the need for compound-specific empirical data.
Topics: Nitrosamines; Carcinogens; Drug Contamination; Humans; Animals; Structure-Activity Relationship; Risk Assessment; Carcinogenicity Tests
PubMed: 38754805
DOI: 10.1016/j.yrtph.2024.105640 -
Saudi Medical Journal May 2024To compare the genotoxic effects of desflurane and propofol using comet assay in patients undergoing elective discectomy surgery. (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
OBJECTIVES
To compare the genotoxic effects of desflurane and propofol using comet assay in patients undergoing elective discectomy surgery.
METHODS
This was a randomized controlled study. Patients who underwent elective lumbar discectomy under general anesthesia with propofol or desflurane were included in the study. Venous blood samples were obtained at 4 different time points: 5 minutes before anesthesia induction (T1), 2 hours after the start of anesthesia (T2), the first day after surgery (T3), and the fifth day following surgery (T4). Deoxyribonucleic acid damage in lymphocytes was assessed via the comet assay.
RESULTS
A total of 30 patients, 15 in each group, were included in the analysis. The groups were similar in terms of age and gender distribution. There were no significant differences in demographics, duration of surgery, total remifentanil consumption, and total rocuronium bromide consumption. The comet assay revealed that head length, head intensity, tail intensity, tail moment at T1 were similar in the desflurane and propofol groups. Head length, tail length and tail moment measured in the desflurane group at T4 were significantly higher compared to the propofol group. Tail lengths of the desflurane group at T1, T2 and T3 were significantly higher than the corresponding values in the propofol group.
CONCLUSION
Propofol and desflurane do not appear to induce DNA damage in lymphocytes. However, when the quantitative data were compared, it was determined that propofol had relatively lower genotoxic potential than desflurane..
Topics: Humans; Propofol; Desflurane; Diskectomy; Comet Assay; Male; Lymphocytes; Female; Adult; Middle Aged; Anesthetics, Inhalation; DNA Damage; Lumbar Vertebrae; Anesthetics, Intravenous; Isoflurane
PubMed: 38734439
DOI: 10.15537/smj.2024.45.5.20240077