scholarly journals Genotoxicity of Marijuana in Mono-Users

2021 ◽  
Vol 12 ◽  
Author(s):  
Eunice Fabian-Morales ◽  
Carmen Fernández-Cáceres ◽  
Adriana Gudiño ◽  
Marco A. Andonegui Elguera ◽  
Karla Torres-Arciga ◽  
...  
Keyword(s):  
Dna Damage ◽  
Illicit Drugs ◽  
Nuclear Division ◽  
Peripheral Blood Lymphocytes ◽  
Control Group ◽  
Chromosomal Damage ◽  
Chromosomal Dna ◽  
Genotoxic Effects ◽  
Nuclear Division Index ◽  
Definition Of

Marijuana (Cannabis sp.) is among the most recurred controlled substances in the world, and there is a growing tendency to legalize its possession and use; however, the genotoxic effects of marijuana remain under debate. A clear definition of marijuana's genotoxic effects remains obscure by the simultaneous consumption of tobacco and other recreational substances. In order to assess the genotoxic effects of marijuana and to prevent the bias caused by the use of substances other than cannabis, we recruited marijuana users that were sub-divided into three categories: (1) users of marijuana-only (M), (2) users of marijuana and tobacco (M+T), and (3) users of marijuana plus other recreative substances or illicit drugs (M+O), all the groups were compared against a non-user control group. We quantified DNA damage by detection of γH2AX levels and quantification of micronuclei (MN), one of the best-established methods for measuring chromosomal DNA damage. We found increased levels of γH2AX in peripheral blood lymphocytes from the M and M+T groups, and increased levels of MNs in cultures from M+T group. Our results suggest a DNA damage increment for M and M+T groups but the extent of chromosomal damage (revealed here by the presence of MNs and NBuds) might be related to the compounds found in tobacco. We also observed an elevated nuclear division index in all marijuana users in comparison to the control group suggesting a cytostatic dysregulation caused by cannabis use. Our study is the first in Mexico to assess the genotoxicity of marijuana in mono-users and in combination with other illicit drugs.

scholarly journals Therapeutic effects of statins on chromosomal DNA damage of dyslipidemic patients

2019 ◽  
Vol 244 (13) ◽  
pp. 1089-1095 ◽  
Author(s):  
Hamiyet Donmez-Altuntas ◽  
Fahri Bayram ◽  
Ayse N Coskun-Demirkalp ◽  
Osman Baspınar ◽  
Derya Kocer ◽  
...  
Keyword(s):  
Dna Damage ◽  
Statin Therapy ◽  
Oxidative Dna Damage ◽  
Nuclear Division ◽  
Statin Treatment ◽  
Therapeutic Effects ◽  
Chromosomal Dna ◽  
Control Subjects ◽  
Before And After ◽  
Nuclear Division Index

Statins are a group of cholesterol lowering drugs and frequently used in the therapy of dyslipidemia. Our knowledge of the impact of statin therapy on DNA damage is as yet rudimentary. In this study, we aimed to assess the possible (1) genotoxic, cytostatic, and cytotoxic effects of statins in peripheral blood lymphocytes by using the cytokinesis-block micronucleus cytome (CBMN-cyt) assay, and (2) oxidative DNA damage by measuring plasma 8-hydroxy-2′-deoxyguanosine (8-OHdG) levels in response to statin therapy. Thirty patients with dyslipidemia who had no chronic diseases and did not use any medicines that interfere lipid values and twenty control subjects were included in the study. Statin therapy was initiated at risk-stratified doses. Blood samples were taken before and after treatment with statins and from control subjects, and CBMN-cyt assay parameters and 8-OHdG levels were evaluated. The chromosomal DNA damage (micronuclei and nucleoplasmic bridges [NPBs]), cytostasis (nuclear division index [NDI]), and cytotoxicity (apoptotic and necrotic cell frequencies) were decreased in patients with dyslipidemia after statin treatment. No significant differences were found for 8-OHdG levels between patients with dyslipidemia before or after statin therapy. The total cholesterol and low-density lipoprotein-cholesterol levels showed positive correlations with NPB frequency in patients with dyslipidemia prior to statin treatment. The present study is the first to evaluate CBMN-cyt assay biomarkers and 8-OHdG levels in patients with dyslipidemia before and after treatment with statins. The observed reductions of chromosomal DNA damage and NDI values with statin treatment could represent an important and under-appreciated pleiotropic effect of these agents. Impact statement In literature, it is possible to find some in vitro cytokinesis-block micronucleus (CBMN) assay studies about human lymphocytes and statins. But, there are no data on CBMN-cytome (CBMN-cyt) assay parameters related to statin therapy in patients with dyslipidemia. The present study is the first to evaluate CBMN-cyt assay biomarkers and 8-OHdG levels in patients with dyslipidemia before treatment and after treatment with statins (5–10 mg/day rosuvastatin or 10–20 mg/day atorvastatin). In this study we show that statin therapy decreased chromosomal DNA damage (micronuclei and nucleoplasmic bridges) and nuclear division index (NDI) values in patients with dyslipidemia by possible molecular reasons independent of oxidative DNA damage. In addition, the decrease of chromosomal DNA damage and NDI values with statin treatment could be indicated by the association between statin use and reduced risk of cancer.

scholarly journals Association between H3K36me3 modification and methylation of LINE-1 and MGMT in peripheral blood lymphocytes of PAH-exposed workers

2020 ◽  
Vol 9 (5) ◽  
pp. 661-668
Author(s):  
Xiumei Xing ◽  
Zhini He ◽  
Ziwei Wang ◽  
Ziying Mo ◽  
Liping Chen ◽  
...  
Keyword(s):  
Dna Damage ◽  
Coke Oven ◽  
Peripheral Blood Lymphocytes ◽  
Exposed Group ◽  
Control Group ◽  
Exposure Level ◽  
Mgmt Expression ◽  
Exposed Workers ◽  
Pah Exposure ◽  
Genome Level

Abstract To explore the epigenetic alterations in response to DNA damage following polycyclic aromatic hydrocarbons (PAHs) exposure and the crosstalk between different epigenetic regulations, we examined trimethylated Lys 36 of histone H3 (H3K36me3) and methylation of ‘long interspersed element-1 (LINE-1)’ and ‘O 6-methylguanine-DNA methyltransferase (MGMT)’ in peripheral blood lymphocytes (PBLCs) of 173 coke oven workers (PAH-exposed group) and 94 non-exposed workers (control group). The PAH-exposed group showed higher internal PAH exposure level, enhanced DNA damage and increased MGMT expression (all P < 0.001). Notably, the methylation of LINE-1 and MGMT decreased by 3.9 and 40.8%, respectively, while H3K36me3 level was 1.7 times higher in PBLCs of PAH-exposed group compared to control group (all P < 0.001). These three epigenetic marks were significantly associated with DNA damage degree (all P < 0.001) and PAH exposure level in a dose–response manner (all P < 0.001). LINE-1 hypomethylation is correlated with enhanced H3K36me3 modification (β = −0.198, P = 0.002), indicating a synergistic effect between histone modification and DNA methylation at the whole genome level. In addition, MGMT expression was positively correlated with H3K36me3 modification (r = 0.253, P < 0.001), but not negatively correlated with MGMT methylation (r = 0.202, P < 0.05). The in vitro study using human bronchial epithelial cells treated with the organic extract of coke oven emissions confirmed that H3K36me3 is important for MGMT expression following PAH exposure. In summary, our study indicates that histone modification and DNA methylation might have synergistic effects on DNA damage induced by PAH exposure at the whole genome level and H3K36me3 is more essential for MGMT expression during the course.

Genetic variation and risk of DNA damage in peripheral blood lymphocytes of Iranian formaldehyde-exposed workers

2017 ◽  
Vol 37 (7) ◽  
pp. 690-696
Author(s):  
Rezvan Zendehdel ◽  
Parviz Abdolmaleki ◽  
Fatemeh Javani Jouni ◽  
Mohammad Mazinani
Keyword(s):  
Dna Damage ◽  
Peripheral Blood ◽  
Human Peripheral Blood ◽  
Peripheral Blood Lymphocytes ◽  
Control Population ◽  
Control Group ◽  
Special Role ◽  
Effective Parameters ◽  
Blood Lymphocytes ◽  
Exposed Population

Formaldehyde (FA) has given positive results for the genetic damage evaluated in human peripheral blood lymphocytes. Polymorphism plays a special role in the toxicity of chemicals. DNA damage in blood cells was evaluated in workers who were occupationally exposed to FA. This study tested the association of alcohol dehydrogenase III (ADH3) and manganese-superoxide dismutase (Mn-SOD) gene polymorphism, with DNA damage of peripheral blood lymphocytes. Gene polymorphisms were evaluated in 54 workers from melamine dinnerware workshops and 34 workers from dairy production workshops. The control and exposed population were matched based on age, smoking, work history and socioeconomic status. DNA damage was evaluated by alkaline comet assay in the peripheral blood lymphocytes. ADH3 and Mn-SOD genotypes were determined in all workers using polymerase chain reaction–restriction fragment length polymorphism method. DNA damage of lymphocyte cells was significantly higher ( p < 0.001) in the exposed individuals in comparison with the control population. The examinations of the exposed group had revealed significantly higher ( p < 0.01) variant of Val/Val of Mn-SOD compared to control group. In workers with ADH32–2 variant, significantly higher levels of DNA damage ( p < 0.01) were observed than the control population with the same genotype. It could be concluded that enzymes involved in the metabolism of FA and oxidative stress controlling are two important effective parameters for DNA damage of peripheral blood lymphocytes in exposed people. These results are regarded as a pioneer investigation for the management of health risks assessment.

scholarly journals Acute Toxicity and DNA Instability Induced by Exposure to Low Doses of Triclosan and Phthalate DEHP, and Their Combinations, in vitro

2021 ◽  
Vol 12 ◽  
Author(s):  
Nathalia de Assis Aguilar Duarte ◽  
Lindiane Eloisa de Lima ◽  
Flora Troina Maraslis ◽  
Michael Kundi ◽  
Emilene Arusievicz Nunes ◽  
...  
Keyword(s):  
Dna Damage ◽  
Acute Toxicity ◽  
Nuclear Division ◽  
Aquatic Organisms ◽  
Human Cells ◽  
Dna Instability ◽  
Nuclear Division Index ◽  
Mutagenic Effects ◽  
The Impact

Triclosan (TCS) is an antimicrobial agent widely used in personal care products (PCP) and the di-(2-ethyl hydroxy-phthalate) (DEHP) is a chemical compound derived from phthalic acid, used in medical devices and plastic products with polyvinyl chloride (PVCs). As result of their extensive use, TCS and DEHP have been found in the environment and previous studies demonstrated the association between their exposure and toxic effects, mostly in aquatic organisms, but there is a shortage in the literature concerning the exposure of TCS and DEHP in human cells. The aim of the present study was to assess the impact of exposure to TCS and DEHP, as well as their combinations, on biomarkers related to acute toxicity and DNA instability, in HepG2 cells, by use of cytokinesis-block micronucleus cytome (CBMNCyt) assay. For that, the cultures were exposed to TCS, DEHP and combinations at doses of 0.10, 1.0, and 10 μM for the period of 4 h and the parameters related to DNA damage (i.e., frequencies of micronuclei (MN) and nuclear buds (NBUDs), to cell division (i.e., nuclear division index (NDI) and nuclear division cytotoxic index (NDCI) and to cell death (apoptotic and necrotic cells) were scored. Clear mutagenic effects were seen in cells treated with TCS, DEHP at doses of 1.0 and 10 μM, but no combined effects were observed when the cells were exposed to the combinations of TCS + DEHP. On the other hand, the combination of the toxicants significantly increased the frequencies of apoptotic and necrotic cells, as well as induced alterations of biomarkers related to cell viability (NDI and NDCI), when compared to the groups treated only with TCS or DEHP. Taken together, the results showed that TCS and DEHP are also able to induce acute toxicity and DNA damage in human cells.

scholarly journals Assessment of DNA damage through micronucleus studies in subjects exposed to formalin

2021 ◽  
Vol 19 (1) ◽  
pp. 01-05
Author(s):  
K Sriambika ◽  
Keyword(s):  
Dna Damage ◽  
Peripheral Blood ◽  
Micronucleus Assay ◽  
Peripheral Blood Lymphocytes ◽  
International Agency ◽  
Control Group ◽  
Buccal Cells ◽  
Exposed Workers ◽  
The Mean ◽  
The Relationship

Background: Formaldehyde (FA) is the reactive and simplest of all the aldehydes. It is used as a preservative in anatomy, pathology and forensic laboratories. The international agency for research on cancer has classified FA as a carcinogen that can cause nasopharyngeal carcinoma, Leukaemia, Liver and pancreatic cancer. Objective And Method: The aim of the study was to assess the DNA damage in peripheral blood lymphocytes and in buccal cells by Micronucleus assay in Formalin exposed workers of Anatomy, Pathology and Forensic laboratories and compare with the control group, and also to analyze the relationship between frequency of Micronuclei and duration of exposure to formalin. Results: The mean and standard deviation (SD) of micronuclei in peripheral blood of exposed was 8.35 and in controls was 4.18. There was a significant increase in the frequency of MN in exposed group when compared with the comparison group (p<0. 5876). Pearson’s correlation test showed a positive correlation between the years of FA exposure and the number of micronuclei in buccal cells and peripheral blood indicating that DNA damage due to FA was directly proportional to the duration of exposure (r=0.8, 0.9). Conclusion: The present study was done to assess the DNA damage in people who were exposed to FA and a control group not exposed to FA by buccal cell and peripheral blood Micronucleus Assay. There was a significant increase in the MN in people exposed to FA which was directly proportional to the duration of exposure.

scholarly journals Increased Chromosomal and Oxidative DNA Damage in Patients with Multinodular Goiter and Their Association with Cancer

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Hamiyet Donmez-Altuntas ◽  
Fahri Bayram ◽  
Nazmiye Bitgen ◽  
Sibel Ata ◽  
Zuhal Hamurcu ◽  
...  
Keyword(s):  
Dna Damage ◽  
Thyroid Cancer ◽  
Multinodular Goiter ◽  
Oxidative Dna Damage ◽  
Thyroid Nodules ◽  
Clinical Problem ◽  
Peripheral Blood Lymphocytes ◽  
Chromosomal Dna ◽  
Increased Risk ◽  
Cancer Types

Thyroid nodules are a common clinical problem worldwide. Although thyroid cancer accounts for a small percentage of thyroid nodules, the majority are benign. 8-Hydroxy-2′-deoxyguanosine (8-OHdG) levels are a marker of oxidative stress and play a key role in the initiation and development of a range of diseases and cancer types. This study evaluates cytokinesis-block micronucleus cytome (CBMN-cyt) assay parameters and plasma 8-OHdG levels and their association with thyroid nodule size and thyroid hormones in patients with multinodular goiter. The study included 32 patients with multinodular goiter and 18 age- and sex-matched healthy controls. CBMN-cyt assay parameters in peripheral blood lymphocytes of patients with multinodular goiter and controls were evaluated, and plasma 8-OHdG levels were measured. The micronucleus (MN) frequency (chromosomal DNA damage), apoptotic and necrotic cells (cytotoxicity), and plasma 8-OHdG levels (oxidative DNA damage) were significantly higher among patients with multinodular goiter. Our study is the first report of increased chromosomal and oxidative DNA damage in patients with multinodular goiter, which may predict an increased risk of thyroid cancer in these patients. MN frequency and plasma 8-OHdG levels may be markers of the carcinogenic potential of multinodular goiters and could be used for early detection of different cancer types, including thyroid cancer.

scholarly journals Chromosomal damage in peripheral blood lymphocytes from nurses occupationally exposed to chemicals

2013 ◽  
Vol 33 (9) ◽  
pp. 897-903 ◽  
Author(s):  
A Santovito ◽  
P Cervella ◽  
M Delpero
Keyword(s):  
Peripheral Blood ◽  
Peripheral Blood Lymphocytes ◽  
Control Group ◽  
Low Doses ◽  
Chromosomal Damage ◽  
Blood Lymphocytes ◽  
Genome Damage ◽  
Occupationally Exposed ◽  
Index Value ◽  
And Control

In the present study, we evaluated the induced genome damage in peripheral blood lymphocytes from a sample of nurses occupationally exposed to low doses of different chemicals. A comprehensive multi-biomarker approach using cytogenetic endpoints was employed for analyzing chromosomal aberrations (CAs) and sister chromatid exchange (SCE) assay. The study included 20 nurses and 20 control subjects matched in age, gender and smoking habits. Nurses were exposed to different chemicals, such as cytostatic drugs, anaesthetics, formaldehyde and other sterilizing gases. Significant differences were found between exposure group and control group in terms of SCEs frequency ( p < 0.001) but not in terms of replication index value ( p = 0.845) and CAs ( p = 0.236). Regression analyses indicated that the age and the exposure years did not influence the amount of the chromosomal damage among nurses. Vice versa, among controls, a positive correlation was found between the number of SCEs and age. In conclusion, our results suggest that a continuous long-term exposure to low doses of chemicals could result in increased levels of SCEs among nurses. This data emphasize the importance of biomonitoring nurses and other hospital workers handling drugs.

scholarly journals Lymphocyte Proliferation Kinetics in Inhabitant of Takandeang Village, Mamuju: A High Background Radiation Areas in Indonesia

2018 ◽  
Vol 10 (1) ◽  
pp. 66 ◽  
Author(s):  
Dwi Ramadhani ◽  
Siti Nurhayati ◽  
Tur Rahardjo ◽  
Mukh Syaifudin
Keyword(s):  
Mitotic Index ◽  
Nuclear Division ◽  
Background Radiation ◽  
Imaging System ◽  
Control Group ◽  
High Background ◽  
Study Results ◽  
Nuclear Division Index ◽  
The Mean ◽  
Radiation Area

BACKGROUND: Mamuju area in West Sulawesi considered as the high natural background radiation area in Indonesia. Our previous study showed that the mean mitotic index (MI) and nuclear division index (NDI) in lymphocytes of Botteng Village, Mamuju inhabitants was lower compared to control samples. To validate our previous study results, here in this study the evaluation of cell proliferation markers which were MI and NDI in peripheral blood lymphocytes (PBL) of Takandeang Village inhabitants was conducted.METHODS: A total 60 people were enrolled in this study, consisted of 35 samples from Takandeang Sub-Village and 25 from normal background radiation area. MI was calculated manually and automatically using Metafer 3.11.2 imaging system. The NDI defined as proportion of mononucleated, binucleated, trinucleated and tetranucleated cells were conducted using cytokinesis block micronucleus (CBMN) assay.RESULTS: The results of this study showed that the mean manual MI in Takandeang Sub-Village inhabitants was lower compared to control group (4.96±2.25 vs. 5.93±2.14). In contrast, the mean automatic MI (20.37±10.49 vs. 18.87±7.49) and NDI (1.555±0.174 vs. 1.523±0.112) in Takandeang Sub-Village inhabitants was higher compared to the control group. Statistical analysis revealed that the difference of mean manual MI, automatic MI and NDI in Takandeang Sub-Village inhabitants was not significantly different compared to the control group(p>0.05).CONCLUSION: It can be concluded that based on this study the chronic low radiation dose exposure in Takandeang Sub-Village, Mamuju has no significant effect on the lymphocytes proliferation.KEYWORDS: lymphocytes, mitotic index, nuclear division index, high background radiation

scholarly journals Evaluation of GammaH2AX in Buccal Cells as a Molecular Biomarker of DNA Damage in Alzheimer’s Disease in the AIBL Study of Ageing

Life ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 141
Author(s):  
Mohammad Sabbir Siddiqui ◽  
Maxime Francois ◽  
Stephanie Rainey-Smith ◽  
Ralph Martins ◽  
Colin L. Masters ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Dna Damage ◽  
Laser Scanning ◽  
Area Under The Curve ◽  
Buccal Cell ◽  
Control Group ◽  
Cell Nuclei ◽  
Chromosomal Dna ◽  
And Control

In response to double-stranded breaks (DSBs) in chromosomal DNA, H2AX (a member of histone H2A family) becomes phosphorylated to form γH2AX. Although increased levels of γH2AX have been reported in the neuronal nuclei of Alzheimer’s disease (AD) patients, the understanding of γH2AX responses in buccal nuclei of individuals with mild cognitive impairment (MCI) and AD remain unexplored. In the current study, endogenous γH2AX was measured in buccal cell nuclei from MCI (n = 18) or AD (n = 16) patients and in healthy controls (n = 17) using laser scanning cytometry (LSC). The γH2AX level was significantly elevated in nuclei of the AD group compared to the MCI and control group, and there was a concomitant increase in P-trend for γH2AX from the control group through MCI to the AD group. Receiver-operating characteristic curves were carried out for different γH2AX parameters; γH2AX in nuclei resulted in the greatest area under the curve value of 0.7794 (p = 0.0062) with 75% sensitivity and 70% specificity for the identification of AD patients from control. In addition, nuclear circularity (a measure of irregular nuclear shape) was significantly higher in the buccal cell nuclei from the AD group compared with the MCI and control groups. Additionally, there was a positive correlation between the nuclear circularity and γH2AX signals. The results indicated that increased DNA damage is associated with AD.

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