DNA Damage In Leukocytes Research Articles

Assessment of the degree of DNA damage in leukocytes of patients with chronic obstructive pulmonary disease

Assessment of the degree of DNA damage in leukocytes of patients with chronic obstructive pulmonary disease

Systemic DNA Damage and Repair Activity Vary by Race in Breast Cancer Survivors.

Non-Hispanic Black breast cancer survivors have poorer outcomes and higher mortality rates than White survivors, but systemic biological mechanisms underlying these disparities are unclear. We used circulating leukocytes as a surrogate for measuring systemic mechanisms, which might be different from processes in the target tissue (e.g., breast). We investigated race-based differences in DNA damage and repair, using a novel CometChip assay, in circulating leukocytes from breast cancer survivors who had completed primary cancer therapy and were cancer free. We observed novel race-based differences in systemic DNA damage and repair activity in cancer survivors, but not in cells from healthy volunteers. Basal DNA damage in leukocytes was higher in White survivors, but Black survivors showed a much higher induction after bleomycin treatment. Double-strand break repair activity was also significantly different between the races, with cells from White survivors showing more sustained repair activity compared to Black leukocytes. These results suggest that cancer and cancer therapy might have long-lasting effects on systemic DNA damage and repair mechanisms that differ in White survivors and Black survivors. Findings from our preliminary study in non-cancer cells (circulating leukocytes) suggest systemic effects beyond the target site, with implications for accelerated aging-related cancer survivorship disparities.

DNA Damage in Bat Blood Leukocytes Using a Chromatin Dispersion Test (CDT): Biomarker of Environmental Genotoxicity.

Environmental pollutants produce adverse effects on organisms and ecosystems. Biomonitoring and biomarkers offer a reasonable approach to make these assessments. Induced genetic changes can be using as a biomarker in organisms that react to a given compound in the ecosystem. Monitoring environmental genotoxicity necessitates the choice of model animals known as "sentinels or biological monitors" and the suitability of validated tests for DNA damage evaluation. We aimed to estimate the DNA damage produced by thermal stress in the leukocytes of the Mexican free-tailed bat (Tadarida brasiliensis). The DNA damage in bat leukocytes exposed to different temperatures (35°C, 45°C, and 55°C) was evaluated by the adapted chromatin dispersion test (CDT) and the results were confirmed by the alkaline comet test. The CDT permitted a clear representation of leukocytes with fragmented DNA and of nonfragmented DNA. In addition, we detected nuclear anomalies in relation to cell death cellular swelling, nuclear fragmentation, and chromatin lysis. The alkaline comet assay revealed that the halos of diffuse chromatin include fragmented DNA. The assay of the method employing the CDT is well established, precise, and cost-effective for the routine quantitative analysis of DNA damage on the effect of the leukocytes of bats exposed to thermal stress. This could also apply as a sensitive screening tool for the evaluation of genotoxicity in environmental protection programs.

Evaluación del daño en el ADN inducido por quimioterapia metronómica en leucocitos de sangre periférica de pacientes caninos con cáncer de mama mediante el ensayo cometa alcalino

Mammary cancer is a disease that requires effective treatments. Conventional chemotherapy, while effective, often causes harmful side effects. In contrast, metronomic chemotherapy (mCHT), which involves the continuous administration of low doses of anticancer drugs, is presented as a less aggressive alternative. In this study, the genotoxic impact of treatment with Cyclophosphamide and Meloxicam under the mCHT approach was evaluated in ten canine (Canis lupus familiaris) patients with mammary carcinoma after undergoing mastectomy. The patients underwent monthly evaluations, including chest X–rays, blood tests, and the alkaline comet assay to measure genotoxic effects of the antineoplastic drugs. These results were compared with those of a group that received conventional chemotherapy. The results revealed that patients treated with mCHT experienced significantly lower levels of DNA damage compared to those who received conventional chemotherapy. Furthermore, DNA damage decreased over time during mCHT, suggesting that dogs may have developed tolerance to the treatment. Blood parameters remained stable in the mCHT–treated group, and X–rays showed no signs of recurrence or metastasis. All dogs survived during the one–year follow–up without mammary cancer recurrence. It is concluded that mCHT with Cyclophosphamide appears to be a less aggressive therapeutic option with a more favorable genotoxic profile in the treatment of mammary cancer in dogs.

In Vivo Cytotoxic, Genotoxic and Radiosensitizing Effects of Clofarabine.

ClFdA is a second-generation antineoplastic agent that has demonstrated significant anticancer activity, particularly against acute lymphoblastic leukemia and has been shown to have radiosensitizing activity. The aim of the study was to explore the genotoxic, cytotoxic and radiosensitizing effects of clofarabine (ClFdA) on bone marrow cells (BMCs), normoblasts and leukocytes of mice in vivo. Cytotoxicity was determined by the reduction in reticulocytes (RET), and genotoxicity was determined by the induction of micronucleated reticulocytes (MN-RET) in the peripheral blood and by DNA break induction in leukocytes determined by single-cell gel electrophoresis (SCGE). The radiosensitizing capacity of ClFdA was determined in leukocytes and BMCs by SCGE. Two mechanisms of MN-RET induction were identified according to the antecedents, that could be due to inhibition of DNA synthesis and demethylation of G-C regions, and subsequent chromosome fragility. ClFdA cytotoxicity causes two contiguous peaks, an early peak that seems to inhibit MN-RET induction and a second peak that seems to be caused by ribonucleotide reductase (RR) and/or DNA synthesis inhibitions. ClFdA induced early DNA damage in noncycling leukocytes, and also radiosensitizes leukocytes immediately after treatment. ClFdA-ionizing radiation (IR) causes two time-dependent episodes of DNA damage, the latest after 80 min triggers a major breakage of DNA. In terms of the number of damaged cells, leukocytes and BMCs are similarly sensitive to ionizing radiation; BMCs are slightly more sensitive than leukocytes to ClFdA, but BMCs are doubly sensitive to combined treatment. ClFdA causes early DNA damage and radiosensitivity in non-proliferating leukocytes, which rules out the most favored hypotheses of the participation of RR and DNA polymerase inhibition.

“Slow kill” treatment reduces DNA damage in leukocytes of dogs naturally infected with Dirofilaria immitis

Parasitic diseases are considered to be a cause of oxidative stress which leads to oxidative damage of various molecules including DNA. This can result in mutations, replication errors, and genome instability. Therefore, aim of this study was to measure DNA damage induced by Dirofilaria immitis in the single cells such as dogs’ leukocytes using the comet assay. Also, we monitored the effects of antiparasitic treatment on mitigation of sensitivity to DNA damage in leukocytes treated with H2O2 using the in vivo and ex vivo comet assay. The whole blood samples from 34 dogs from Serbia were used, both males and females, from one to 13 years old, both pure and mixed-breeds. A rapid immunochromatographic test (Antigen Rapid Heartworm Ag 2.0 Test Kit, Bionote, Minnesota, USA) was used for the detection of D. immitis antigens. The modified Knott’s test and PCR were used in the aim of detecting D. immitis microfilariae in dogs’ blood, and evaluating the number of circulating microfilariae during the treatment. The genotoxicity evaluation showed that D. immitis infection resulted in DNA damage in naturally infected dogs, with the highest DNA damage occurring in the group of dogs with severe clinical signs. Treatment with ivermectin and doxycycline decreased DNA damage in leukocytes of dogs in all groups, as the intensity of infection decreased due to applied therapy. Ex vivo comet assay results showed that leukocytes exhibited decreased sensitivity to H2O2-induced DNA damage during treatment. The results of the modified Knott’s test and PCR in our study showed that treatment with ivermectin and doxycycline was successful in decreasing the average number of microfilariae during the time and at the end eliminating them from the dogs’ blood.

Disturbed Antioxidant Capacity in Patients with Systemic Sclerosis Associates with Lung and Gastrointestinal Symptoms.

The correct balance between reactive oxygen species and antioxidant defense in an organism is disturbed in oxidative stress. To assess oxidative balance in 36 SSc patients and 26 healthy controls (HCs), we measured reactive oxidative metabolites (ROMs), total antioxidant capacity (TAC), lipid peroxidation (measuring 4-HNE), and DNA oxidative damage (measuring 8-OHdG) in serum. Furthermore, DNA breaks in leukocytes of 35 SSc patients and 32 HCs were evaluated using COMET. While we report high ROMs for both SSc patients and age/sex matched HC samples, there was a significant increase in TAC in SSc patients as compared to HCs, and thus also a significantly higher oxidative stress index in SSc patients. TAC was significantly higher in SSc patients with ILD and gastrointestinal involvement, as well as in patients with anti-topoisomerase antibodies. We observe no difference in serum lipid peroxidation status or oxidative DNA damage. However, SSc patients had significantly more leukocyte DNA breaks than HCs; the most damage was observed in patients treated with immunosuppressives. Thus, our study confirms presence of oxidative stress and increased DNA damage in leukocytes of SSc patients; however, it points toward increased antioxidant capacity, which needs to be further studied.

DNA strand break levels in cryopreserved mononuclear blood cell lines measured by the alkaline comet assay: results from the hCOMET ring trial.

The comet assay is widely used in biomonitoring studies for the analysis of DNA damage in leukocytes and peripheral blood mononuclear cells. Rather than processing blood samples directly, it can be desirable to cryopreserve whole blood or isolated cells for later analysis by the comet assay. However, this creates concern about artificial accumulation of DNA damage during cryopreservation. In this study, 10 laboratories used standardized cryopreservation and thawing procedures of monocytic (THP-1) or lymphocytic (TK6) cells. Samples were cryopreserved in small aliquots in 50% foetal bovine serum, 40% cell culture medium, and 10% dimethyl sulphoxide. Subsequently, cryopreserved samples were analysed by the standard comet assay on three occasions over a 3-year period. Levels of DNA strand breaks in THP-1 cells were increased (four laboratories), unaltered (four laboratories), or decreased (two laboratories) by long-term storage. Pooled analysis indicates only a modest positive association between storage time and levels of DNA strand breaks in THP-1 cells (0.37% Tail DNA per year, 95% confidence interval: -0.05, 0.78). In contrast, DNA strand break levels were not increased by cryopreservation in TK6 cells. There was inter-laboratory variation in levels of DNA strand breaks in THP-1 cells (SD = 3.7% Tail DNA) and TK6 reference sample cells (SD = 9.4% Tail DNA), whereas the intra-laboratory residual variation was substantially smaller (i.e. SD = 0.4%-2.2% Tail DNA in laboratories with the smallest and largest variation). In conclusion, the study shows that accumulation of DNA strand breaks in cryopreserved mononuclear blood cell lines is not a matter of concern.

Prophylactic consequences of sodium salicylate nanoparticles in cisplatin-mediated hepatotoxicity

Unintended side effects linked to the antineoplastic drug cisplatin are a major drawback in its clinical application. The underlying source of these side effects include the generation of reactive oxygen species which are toxic and damaging to tissues and organs. In the present study the anti-inflammatory and antioxidant potential of sodium salicylate was assessed against cisplatin-induced hepatotoxicity in albino rats. Sodium salicylate was used as a model drug and loading into hollow structured porous silica using ultrasound-assisted sol–gel method to produce a nanoemulsion. Transmission Electron Microscopy and Dynamic Light scattering analysis were employed to assess the structural properties and stability of this model. Liver function was assessed by measuring biomarkers including ALT, AST & GGT and oxidant/antioxidant markers including MDA, NO, PON, GSH, MCP1 & AVP in serum or liver tissue. Additionally, blood leukocyte DNA damage was evaluated. Cisplatin significantly altered the normal levels of all biomarkers confirming its hepatotoxic effects. In contrast, treatment with sodium salicylate-loaded silica nanoemulsion significantly restored the levels of these markers. The finding suggests the protective effects of this model drug in preventing cisplatin-induced hepatotoxicity, and therefore may have implications in attenuating cisplatin-induced hepatotoxicity.

Genotoxicity of waterpipe smoking in young adults from Sarajevo, Bosnia & Herzegovina

BackgroundWaterpipe, also known as a hookah or narghile, is a type of tobacco products consumption device. Recently it has been increasingly popular in Bosnia and Herzegovina and the region. Waterpipe consumers are predominantly adolescents and young adults. Many of them believe in slighter harmful effects of waterpipes, compared to cigarettes. We aimed to determine the DNA damage in oral leukocytes and buccal cells of young individuals who have smoked a waterpipe for more than one year. MethodsThe study group consisted of 40 cigarette non-smokers who regularly smoked a waterpipe on average of once per week. As a control, 40 non-smoking individuals were selected to match smokers for age. All participants in the study were healthy male and female adults from Bosnia and Herzegovina, 18–30 years of age. Before sampling, detailed survey and informed consent have been provided by each participant. Comet assay in oral leukocytes and buccal micronucleus cytome (BMCyt) assay in exfoliated buccal cells were applied. ResultsAlmost half of waterpipe smokers (WPS) tasted waterpipe at 15–16 years of age. Comet assay analysis showed increased tail intensity, tail length, and tail moment values among WPS compared to non-smokers (NS) (p = 0.0001, p = 0.0067, and p = 0.0001, respectively). Frequencies of the micronucleated (p = 0.0004), binucleated (p = 0.01), karyorrhectic, (p = 0.0036), and pycnotic cells (p = 0.03) were significantly higher in WPS compared to NS group. ConclusionsGenotoxicity and DNA damage biomarkers were increased in oral leukocytes and exfoliated buccal cells of young waterpipe smokers from Bosnia and Herzegovina, compared to NS group.

Comparison of the dynamics of DNA damage in blood leukocytes and survival of mice after total body irradiation with Bragg peak carbon ions or x-rays

This study has determined a survival rate of mice irradiated with accelerated carbon ions (450 MeV/nucleon) in the Bragg peak or X-ray at a dose of 6.5 Gy, using the comet assay. Levels of DNA damage (%TDNA) in blood leukocytes from mice were measured 1 day before, 1-23 days after exposure to carbon ions and 1-28 days after exposure to X-ray radiation at the same dose. According to survival and % TDNA parameters, it was found that a damaging effect of carbon ions is greater than that of X-rays and substantial variations in % TDNA, which occur in individual animals, could appear to cause individual differences in the development of genome instability in the long term. It is assumed that a higher % TDNA in leukocytes after carbon ion exposure compared to that of X-rays, a wide range of variations and asynchronous changes in individuals in the post-irradiation period are associated with the induction of clustered DNA damages and mitochondrial dysfunction, and are also due to genetic and epigenetic factors. The results obtained point to the need to assess the state of blood leukocytes in animals with a heterogeneous genetic background using the comet assay before irradiation in order to form a group with similar %TDNA values. The revealed differences in individual laboratory animals require further study in order to improve animal models in the light of the development of personalized biomedicine.

Comparison of the Dynamics of DNA Damage in Blood Leukocytes and Survival Rate of Mice after Total Body Irradiation with Carbon Ions in the Bragg Peak or X-Rays

Comparison of the Dynamics of DNA Damage in Blood Leukocytes and Survival Rate of Mice after Total Body Irradiation with Carbon Ions in the Bragg Peak or X-Rays

Clinical Investigation of Leukocyte DNA Damage in COVID-19 Patients

This prospective cross-sectional study aimed to evaluate leukocyte DNA damage in coronavirus disease (COVID-19) patients. In this study, 50 COVID-19-positive patients attending the Erzurum City Hospital Internal Medicine Outpatient Clinic and 42 control group patients were included. DNA damage was detected in living cells through leukocyte isolation in 50 COVID-19-positive patients using the comet assay method. DNA tail/head (olive) moments were evaluated and compared. White blood cells (WBC), red blood cells (RBC), hemoglobin (HGB), neutrophils (NEU), lymphocytes (LYM), eosinophils (EO), monocytes (MONO), basophils (BASO), platelets (PLT), and the neutrophil/lymphocyte ratio (NLR) were analyzed. The RBC, lymphocyte, eosinophil, and monocyte means were significantly higher in the control group (p < 0.05), whereas the HGB and neutrophile means were significantly higher in the study group (p < 0.05). There were significant negative correlations between COVID-19 and RBC (r = -0.863), LYM (r = -0.542), EO (r = -0.686), and MONO (r = -0.385). Meanwhile, there were significant positive correlations between COVID-19 and HGB (r = 0.863), NEU (r = 0.307), tail moment (r = 0.598), and olive moment (r = 0.582). Both the tail and olive moment mean differences were significantly higher in the study group, with higher ranges (p < 0.05). COVID-19 infection caused statistically significant increases in both the tail and olive damage percentage in patients, causing DNA damage. Lastly, the NLR rate was associated with the presence and progression of COVID-19.

Активность сукцинат- и лактатдегидрогеназы лимфоцитов, индуцированные АФК нейтрофилов и повреждение ДНК лейкоцитов в крови облучённых ионами углерода мышей

At the present time, the studies carried out to improve the radiotherapy of tumors using accelerated heavy ions are of great interest, since they give off the main energy at the end of the run at the Bragg peak, which increases the severity of radiation damage to the tumor and minimizes damage to surrounding healthy tissues. In this work, the levels of lymphocyte lactate dehydrogenase (LDH) and succinate dehydrogenase (SDH) activity, the ratio of LDH/SDH, induced reactive oxygen species (ROS) of neutrophils, and leukocytes DNA damage (%TDNA) in blood 1 day after accelerated carbon ions irradiation of mice with an energy of 450 MeV/nucleon in doses of 0.2-2 Gy in the Bragg peak were determined. Found: SDH activity increased at doses of 0.2-1 Gy and sharply decreased at a dose of 1.5 Gy in all mice. With a decrease in SDH activity, glycolysis (LDH activity) increased compensatory, which, apparently, is associated with the developing mitochondrial dysfunction of immune cells. The %TDNA of leukocytes increased depending on the dose and was accompanied by a decrease in the functional activity of neutrophils - the zymosan-induced ROS production decreased. Thus, against the background of an increased %TDNA and a decrease in SDH activity, glycolysis becomes of great importance. The applied methods are highly sensitive and can be used to detect individual differences in animals that are biological models in preclinical studies.

The association between gestational diabetes mellitus and DNA damage in umbilical cord leukocytes and placental samples

Objective(s): To evaluate the relation between gestational diabetes mellitus (GDM) and maternal and/or fetal DNA integrity. Method: 59 pregnant women were classified into two groups on the basis of 75 g oral glucose tolerance test (OGTT) and glycemic profile (GP): Control group (OGTT and GP normal, n = 29) and GDM group (abnormal 75 g OGTT, n = 30). The umbilical cord blood and placental samples obtained from the maternal side were collected at the time of delivery. Alkaline comet assay was performed for the determination of DNA damage. The trial was approved with the protocol number 72867572.050.01.04-299082. Result(s): Body mass index (BMI), weight gain during pregnancy, glycemic means and fetal weight were increased in GDM group compared control group (p = .01, .0001, .04, and .01, respectively). In the GDM group, the number of large-for-gestational-age (LGA) infants was significantly higher compared to the nondiabetic group (p = .04). Tail DNA percentages in placental samples were higher in the GDM group compared to controls (p = .01); however, DNA integrity in umbilical cord leukocytes was similar between the groups (p = 0.1). In contrast to umbilical cord DNA damage, placental DNA damage showed positive correlation with maternal glycemia in the whole group and within each group. The positive association of placental DNA damage and GDM remained after adjusting for age, BMI, smoking, glycemia, gestational age at delivery, fetal weight at delivery, and delivery type (p = .01). Conclusion(s): Placental DNA damage is associated with GDM and placental cells seem to be more vulnerable to DNA damage compared to fetal blood cells.

Beneficial effects of vitamin B12 treatment in pediatric patients diagnosed with vitamin B12 deficiency regarding total-native thiol, oxidative stress, and mononuclear leukocyte DNA damage

Vitamin B12 is involved in biochemical metabolic pathways. B12 deficiency is common in childhood when the need for the vitamin increases and growth and development occur. Various hematological, neurological, psychiatric, and gastrointestinal disorders are observed in its deficiency. In addition, B12 deficiency is associated with oxidative stress and DNA damage. Therefore, the aim of our study is to evaluate oxidative stress, thiol/disulfide homeostasis, and DNA damage pre and post-treatment in children diagnosed with B12 deficiency. A total of 40 children with B12 deficiency were included in the study after the consent form was approved. Blood was drawn from children pre and posttreatment. Hemoglobin (HGB), hematocrit (HCT), and red blood cells (RBC) were measured by autoanalyzer; total antioxidant status (TAS), total oxidant status (TOS), total thiol (TT), and native thiol (NT) were measured by the photometric method, and DNA damage was analyzed by the comet assay method. Oxidative stress index (OSI) and disulfide (DIS) values were calculated. As a result of the experiments, HGB, HCT, and RBC increased with treatment. While TAS, TT, and NT as antioxidant parameters increased; TOS, OSI, and DIS decreased with treatment compared to pretreatment. DNA damage was also found to decrease with treatment. Additionally, these data were statistically significant (p < 0.001). It was found that oxidative stress and DNA damage decreased with oral B12 treatment in children with B12 deficiency, and clinical parameters were also improved.

Lantana undulata Schrank – A New Source of Biological Potential in the Verbenaceae Family

Background : The presence of condensed tannins, flavonones, flavonols, flavones, xantones, catechins and alkaloids in the ethanolic extract of Lantana undulata leaves has been associated with cytotoxicity and virucidal effect on suid herpesvirus. Objective: To evaluate cellular toxicity, antimicrobial and antioxidant activities, and anti-phlogistic property of the ethanolic extract leaves of Lantana undulata, a plant from the Verbenaceae family. Method: Cytotoxicity was evaluated on Madin Darby bovine kidney (MDBK) cells and erythrocytes and through leukocyte DNA damage. Antibacterial and antifungal activities were performed using the agar diffusion technique and broth microdilution. The inhibition percentage and viral inhibition index were established against bovine herpesvirus. The antioxidant effect (EC50) was determined by the DPPH technique and the mouse ear edema model was used to determine the anti-phlogistic activity. Results: The maximum nontoxic concentration for MDBK cells was 650 μg/ml. The ethanolic extract of L. undulata was considered non-hemolytic from 2 to 16 μg/ml and not genotoxic at the concentration tested (&lt;8 μg/ml). High concentrations (3500 μg/ml) were needed to inhibit bacteria and yeasts, and the action of the extract was bacteriostatic or fungistatic. The IIV was of 0.37 and the IP was of 57.34% against bovine herpesvirus. The antioxidant EC50 was 540.87 μg/ml and the reduction of oedema occurred at 10, 30 and 100 mg/kg in the mouse model used. Conclusion: Although the ethanolic extract of L. undulataleaves showed to be potentially toxic and to have a reduced spectrum of action on microorganisms, the outstanding antiphlogistic action puts the therapeutic potential of this plant into perspective.

Comparative Study of DNA Damage in Mouse Blood Leukocytes and MDA-MB-231 Human Breast Adenocarcinoma Cells Induced by Various Concentrations of Ozone, Hydrogen Peroxide, and Gemcitabine

Comparative Study of DNA Damage in Mouse Blood Leukocytes and MDA-MB-231 Human Breast Adenocarcinoma Cells Induced by Various Concentrations of Ozone, Hydrogen Peroxide, and Gemcitabine

The impact of Technetium-99m dimercapto-succinic acid scintigraphy on DNA damage and oxidative stress in children.

Technetium-99m-dimercapto succinic acid (Tc-99m DMSA) scintigraphy is a commonly used imaging modality in children with urological abnormalities. The radiopharmaceuticals, which have the effects of ionising radiation, are used in this method. This study aimed to investigate the impact of the Tc-99m DMSA scan on renal oxidative stress and mononuclear leukocyte (MNL) DNA damage. Children, who were followed up by paediatric nephrology at Bezmialem Vakif University and underwent Tc-99m DMSA scintigraphy between April 2015 and January 2016 with the indication of detection of renal scars, were included in this study. The exclusion criteria were nephrolithiasis, history of premature birth and recent urinary tract infection 3months prior to scintigraphy or antibiotic use in the last 1month. 3mL heparinised blood samples were obtained just before, immediately after and 1week after the scintigraphy. MNL DNA damage, total antioxidant status (TAS) and total oxidant status (TOS) were measured in the blood samples. The oxidative stress index (OSI) was calculated. Spot urine samples were obtained from each patient before and within 3days after performing the scintigraphy. TAS/Creatinine (TAS/Cr), TOS/Creatinine (TOS/Cr) and N-acetyl-glucosaminidase/creatinine (NAG/Cr) levels were measured in the urine samples. Twenty-seven children were evaluated. The values between TAS, TOS and OSI levels in serum samples at baseline, immediately after and 1week after the scintigraphy (P=.105, P=.913, and P=.721, respectively) showed no statistically significant difference. The levels of TAS/Cr, TOS/Cr, NAG/Cr ratios and OSI, which were evaluated from urine samples before and within 3days after the scintigraphy scan were also similar (P=.391, P=.543, P=.819 and P=.179, respectively). The levels of DNA damage only increased following scintigraphy scan and decreased a week later (P<.05). The effect of Tc-99m DMSA scintigraphy is insufficient to create oxidative damage, but it can cause DNA damage via the direct impact of ionising radiation which can be repaired again in a short time.

Early maternal separation enhances melanoma progression in adult female mice by immune mechanisms

Maternal separation (MS) is a risk factor for major depressive disorder. Both cancer and depression seem to share a common biological link. Here, we evaluated the progression of melanoma and the underlying mechanisms related to this progression, namely cell proliferation and apoptosis, in adult female mice exposed to MS. Female C57BL/6 mice were exposed to MS for 60 min/day during the first 2 postnatal weeks (here called MS mice) or left undisturbed (here called non-MS mice). Melanoma cells were inoculated subcutaneously into the axillary region of adult animals, and tumor progression was evaluated for 25 days. Adult MS mice presented depressive-like behavior and working memory deficits. MS accelerated murine melanoma growth by mechanisms related to decreased apoptosis and increased cell proliferation rate, such as increased expression of IL-6 and mTOR. MS stimulated eukaryotic elongation factor 2 expression and increased the number of circulating monocytes and DNA damage in peripheral blood leukocytes, an effect associated with oxidative DNA damage. In conclusion, MS accelerated the progression of murine melanoma by mechanisms related to tumor proliferation and apoptosis, revealing a relationship between adverse childhood experiences and cancer progression, particularly melanoma.