Total Number Of Chromosomal Aberrations Research Articles

Protective Effect of Cafestol on Doxorubicin-induced Genotoxicity in Rats

Doxorubicin is an efficient antineoplastic agent that has a broad antitumour spectrum; however, its genotoxic adverse effects on normal cells can be produced through oxidative damage, and this limits its clinical application. Cafestol is a naturally-occurring diterpene in unfiltered coffee with noteworthy antioxidant, antimutagenic and anti-inflammatory activities.
 The present study aimed to investigate the possible protective effect of cafestol against doxorubicin-induced chromosomal and DNA damage in rat bone marrow cells. Wistar
 Albino rats of both sexes were administered cafestol (5mg/kg body weight once daily for 14 consecutive days) by oral gavage alone or with doxorubicin which was injected as a single dose (90 mg/kg intraperitoneally at day 14) to induce toxicity. The bone marrow was harvested 24 hours after doxorubicin’s injection in all groups for the assessment of structural chromosomal aberration, micronucleus, and comet assays. The result showed that rats in the doxorubicin-only group exhibited a significant decrease (P<0.05) in mitotic index with a significant elevation (P<0.05) in the % DNA in Tail, micronucleus appearance and total structural chromosomal aberrations compared to those of the negative control group; while oral administration of cafestol 14 days prior to doxorubicin, significantly-reduced the % DNA in Tail, micronucleus appearance, and the total number of chromosomal aberrations (P<0.05), and improved the mitotic index compared to rats intraperitoneally-injected with doxorubicin alone. 
 This study revealed that cafestol has protective effects against the genotoxicity induced by doxorubicin.

Effects of Contamination by Heavy Metals and Metalloids on Chromosomes, Serum Biochemistry and Histopathology of the Bonylip Barb Fish Near Sepon Gold-Copper Mine, Lao PDR.

The objectives of the present study were to determine the concentrations of heavy metals and metalloids in water, sediment and Osteochilus vittatus fish, and to assess chromosome aberrations, serum biochemical changes and histopathological alterations in O. vittatus from the Nam Kok river near the Sepon gold-copper mine, Lao People’s Democratic Republic compared with the reference area. The results showed that Fe, Mn and Ni in water, As and Cd in sediment as well as As, Cd, Cr, Mn and Ni in O. vittatus muscle samples near the gold-copper mine exceeded standard values. Furthermore, the chromosome assessment in O. vittatus revealed seven types of chromosome aberrations, and the highest total number of chromosome aberrations was a centromere gap. The total number of chromosome aberrations, cell number with chromosome aberrations and percentage of chromosome aberrations in O. vittatus as well as serum liver enzymes between the studied areas were significantly different (p < 0.05). The liver histopathological alterations of the fish near the gold-copper mine revealed atypical cellular structures as nuclear membrane degeneration, rough endoplasmic reticulum disintegration and abnormal cytoplasmic mitochondria. The results of this study suggested that heavy metal and metalloid contaminations from the Sepon gold-copper mine area negatively affect O. vittatus fish in terms of chromosomal defects, serum biochemical changes and liver histopathological appearances.

Evaluation of the cytogenotoxic activity of mercury by analyzing chromosomal aberrations in wheat root meristem cells

The work evaluates the cytogenotoxic effect of mercury by performing a primary screening on a plant object. The authors determined the qualitative and quantitative characteristics of a cytogenotoxic effect depending on the exposure time and the dose of mercury nitrate (Hg (NO3)2) in anaphase and telophase of mitosis on wheat apical meristem cells of the Memory of Aziev variety. In the process of primary screening to assess the cytogenotoxic effect of the test substance, the nature and diversity of chromosomal abnormalities in the wheat meristem cells of the presented variety were studied. The frequency of occurrence of various types of chromosomal aberrations was analyzed. The complex shows the effect of mercury salts on viability indices and chromosomal instability of wheat. The cumulative pathology curves for different exposures of (Hg (NO3)2) are presented. A significant increase in the number of pathologies was shown in accordance with the increase in mercury concentration in anaphase of mitosis. A similar pattern was observed in the change in the total number of chromosome aberrations in accordance with the increase in the soaking time of seed material. The results of the study of the cytogenotoxic activity of mercury make it possible to assess the toxicity of mercury (Hg (NO3)2) for plant objects and recommend the object used in the experiment as an adequate model of test systems for studying xenobiotics.

Effects of tobacco abuse on major chromosomal instability in human papilloma virus 16-positive oropharyngeal squamous cell carcinoma.

A substantial number of patients with oropharyngeal squamous cell carcinoma (OPSCC) have two oncogenic risk factors: Human papilloma virus (HPV) infection and tobacco use. These factors can be competitive or synergistic at the chromosomal and genomic levels, with strong prognostic and therapeutic implications. HPV16 has been shown invitro to be a high‑risk HPV that induces low rates of chromosomal copy number alterations. However, chromosomal instability can be increased by smoking. Evaluating chromosomal instability in HPV‑positive patients according to their smoking status is therefore critical for assessing the prognosis and therapeutic impact. The aim of this study was to assess chromosomal instability in patients with HPV‑positive OPSCC according to smoking status. Chromosomal instability was investigated with array‑based comparative genomic hybridization(aCGH) in 50patients with OPSCC. Differences in chromosomal alterations were examined according to the HPV and smoking status of the patients. HPV‑positive tumors (24/26were HPV16‑positive) had fewer genomic aberrations (P=0.0082) and fewer breakpoints (P=0.048) than HPV‑negative tumors. We confirmed the association between HPV‑positive OPSCC and chromosomal losses at 11q. We verified the association between HPV‑negative OPSCC and losses at 3p and 9p and gains at 7q and 11q13. In the patients with OPSCC who were HPV‑positive, the total number of chromosomal aberrations per tumor was significantly higher in the group of patients who were smokers (P=0.003). However, the cytobands did not differ significantly according to the smoking status. On the whole, the data of this study may help to improve the stratification of HPV‑positive OPSCC patients and must be supplemented by next‑generation sequencing studies in order to describe the mutational and transcriptomic profiles of such patients according to smoking status.

Cytogenetic aspects instability to the genome in newborns from different ecological districts of Ivano-Frankivsk region

Aim. Оf the research work was to establish the frequency and spectrum of chromosomal aberrations, associations of acrocentric chromosomes in infants from different ecological regions of Ivano-Frankivsk region. Methods. Metaphase plates of 187 infants from different ecological districts have been analyzed with the aim to determine the frequency and spectrum of chromosomal aberrations, associations of acrocentric chromosomes in newborns. Results. The obtained results of the frequency of associations of acrocentric chromosomes correlated with the frequency indices of chromosomal aberrations (r correlated from 0.68 to 0.84), that proved the negative influence of ecological living conditions on immunogenetic status and adaptive human capabilities. Conclusions.It was determined that the total number of chromosomal aberrations in newborns from districts of ecological comfort was 2.0 and 2.3 times lower as compared to newborns from zones with chemical and radiation contamination. The frequency of cells with associations of acrocentric chromosomes was 7.8 % higher in children from zones of chemical contamination and 9.9 % from zones of radiation pollution as compared to the children from districts of ecological comfort.&#x0D; Keywords: chromosomal aberrations, associations of acrocentric chromosomes, newborns, ecological zones.

Effect of irradiation on DNA synthesis, NBN gene expression and chromosomal stability in cells with NBN mutations

IntroductionThe NBN gene product is part of the MRE11/RAD50/NBN complex, which plays an essential role in genomic stability. In the study we try to answer the question what is the effect of irradiation on DNA synthesis, NBN gene expression and chromosomal stability in cells with homozygous c.657-661del, and heterozygous c.657-661del, p.I171V and p.R215W NBN gene mutations.Material and methodsImmortalized B-lymphocytes with NBN gene mutations were X-ray irradiated at doses of 1, 2, 5 and 8 Gy/min. Radioresistant DNA synthesis rate and the percentage of cells in phase S was analyzed by 3H thymidine and BrdU incorporation assays. NBN gene expression was quantified by real-time PCR with TaqMan fluorescent probe.ResultsIncreasing the irradiation dose resulted in gradual decrease of 3H thymidine incorporation in all cells, but significantly only in homo- and heterozygous c.657-661del cells (p-values < 0.0001). After irradiation the relative expression of NBN was significantly higher in homozygous c.657-661del and heterozygous p.R215W cells as compared to heterozygous c.657-661del, p.I171V and control cells (p < 0.01). All cells with NBN gene mutations showed significantly higher total number of chromosomal aberrations per metaphase as compared to control cells, with the highest number of aberrations in homozygous c.657-661del cells (p < 0.001).ConclusionsThe results obtained indicate that homozygous c.657-661del mutation affects cell sensitivity to irradiation. Moreover, homozygous variant is associated with disturbance in the activation of cell cycle checkpoints and with defects in DNA repair. In turn, heterozygous c.657-661del, p.R215W and p.I171V mutations do not substantially alter the radiosensitivity.

Incidenca hromozomskih aberacija otkrivenih prenatalno metodom amniocenteze u Opstoj bolnici Uzice u periodu 2006-2014. godine

Objective. The main objective of this paper is to present for the first time results of prenatal diagnosis, the incidence of chromosomal aberrations, in the General Hospital Uzice, with special reference to trisomy 21. Methods. This study included a group of 749 pregnant women who underwent invasive prenatal diagnosis using amniocentesis between September 2006th to the August 2013th at the Department of Gynecology and Obstetrics. The total number of delivered women during the same time period was 12 447. Karyotype analysis of in vitro cultured fetal cells was performed using standard techniques on Cytogenetic Department, Clinical Center Kragujevac. All collected data were analyzed and even acknowledge the graphic. Results. Cytogenetic analysis revealed 29 fetal chromosomal abnormalities (3,9%). From the total number of chromosomal aberrations was revealed 14 unbalanced chromosomal rearrangements (48%) and 15 balanced chromosomal aberrations (52%). The seven trisomy of chromosome 21, one triploidy, one deletion, one duplication, two mosaic trisomies, two numerical aberrations of sex chromosomes were detected. The balanced chromosomal rearrangements revealed 15 inversion of chromosome 9. Trisomy 21 makes 24% of all total chromosomal aberrations and 50% of unbalanced rearrangmants. The incidence of Down syndrome prenatally dijagnostifi kovanog is one of 107 amnion.

Oxidative damage to nucleic acids and benzo(a)pyrene-7,8-diol-9,10-epoxide-DNA adducts and chromosomal aberration in children with psoriasis repeatedly exposed to crude coal tar ointment and UV radiation.

The paper presents a prospective cohort study. Observed group was formed of children with plaque psoriasis (n=19) treated by Goeckerman therapy (GT). The study describes adverse (side) effects associated with application of GT (combined exposure of 3% crude coal tar ointment and UV radiation). After GT we found significantly increased markers of oxidative stress (8-hydroxy-2′-deoxyguanosine, 8-hydroxyguanosine, and 8-hydroxyguanine), significantly increased levels of benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE) DNA adducts (BPDE-DNA), and significantly increased levels of total number of chromosomal aberrations in peripheral lymphocytes. We found significant relationship between (1) time of UV exposure and total number of aberrated cells and (2) daily topical application of 3% crude coal tar ointment (% of body surface) and level of BPDE-DNA adducts. The findings indicated increased hazard of oxidative stress and genotoxic effects related to the treatment. However, it must be noted that the oxidized guanine species and BPDE-DNA adducts also reflect individual variations in metabolic enzyme activity (different extent of bioactivation of benzo[a]pyrene to BPDE) and overall efficiency of DNA/RNA repair system. The study confirmed good effectiveness of the GT (significantly decreased PASI score).

POTENTIAL ANTICLASTOGENIC EFFECT OF HYPERFORIN

Summary Hyperforin is a prenylated phloroglucinol derivative which occurs in the plant Hypericum perforatum L. It has several medicinally important properties (antidepressant, anti-inflammatory, proapoptotic, antibacterial and antiangiogenic). To enable its medicinal use, it is necessary to investigate its potential genotoxic effect on human cell lines. We also observed an anticlastogenic effect of hyperforin towards the indirect mutagen benzo(a)pyrene. Benzo(a)pyrene is a widespread polycyclic aromatic hydrocarbon. We performed experiments on human tumor cell line HepG2, using the in vitro mammalian chromosome aberration test. We investigated two cytogenic parameters: the number of aberrant metaphases and the total number of chromosome aberrations. We found out that hyperforin was not genotoxic on human cell line HepG2. The second part of our results implies that hyperforin had an anticlastogenic effect against the indirect mutagen benzo(a)pyrene in our experimental conditions. In future we will continue our research by using another range of hyperforin concentrations, other cell lines and other chemical mutagens.

Chromosomal aberrations in peripheral blood lymphocytes in patients with newly diagnosed celiac and Crohn’s disease

The aims of this research were to determine the number of chromosomal aberrations in peripheral blood lymphocytes and to evaluate the number of circulating lymphocytes with CD103, integrin expressed on intraepithelial lymphocytes and preserved in enteropathy-associated T-cell lymphoma, in patients with newly diagnosed Crohn's disease, celiac disease, and healthy controls. During the period of 30 months, we included 44 patients. Chromosome aberrations were analyzed in peripheral blood lymphocytes by a single cytogeneticist. Multicolor flow cytometric was used for immunophenotyping of peripheral blood lymphocytes. We found a significantly higher number of chromosomal aberrations/100 metaphases in the celiac and Crohn's disease group compared with the controls (P=0.01) and they also had a significantly higher number of aberrant cells compared with the controls (P<0.001). There was no statistically significant difference between the groups with respect to the percentage of CD103+ and CD8+CD103+ cells between groups (P=0.16 and 0.41, respectively) and no correlation between the total number of chromosomal aberrations and the percentage of CD103+ and CD8+CD103+ cells (P=0.06 and 0.06, respectively). Patients with active celiac and newly diagnosed Crohn's disease, before treatment initiation, have a significantly increased number of chromosomal aberrations in peripheral blood lymphocytes. No dissemination of intraepithelial cells in the blood and correlation to the chromosomal aberration was found.

Genotoxic and Cytotoxic Study of Tecoma stans Bignoniaceae

Tecoma stans (Bignoniaceae) is a central and south American tree used for the control of diabetes. This plant is cultivated in Iraq. The dried leaves were soaked in ethanol and water separately for 3 days then filtered and dried. The genotoxic potential of Tecoma stans was studied by in vivo and in vitro system. This study examined the genotoxic activity of aqueous and ethanolic extracts on bone marrow cells from BALB/c mice through evaluation of mitotic index and chromosomal aberrations and cytotoxic effect of the two extracts on Mouse Embryo Fibroblast (MEF) cell line. No alteration in the total number of chromosomal aberrations or the number of cells with chromosomal aberrations observed and percentage of mitotic index at the concentrations tested remained unchanged. The higher concentrations used of the plant extracts had a cytotoxic effect on the MEF cell line. Both extracts had no significant clastogenic effect in vivo but showed cytotoxic effects on mouse embryo in vitro, caution should be exercised in the use of this substance as a medicine.

Early life stage and genetic toxicity of stannous chloride on zebrafish embryos and adults: Toxic effects of tin on zebrafish

Humans are exposed to stannous chloride (SnCl(2)), known as tin chloride, present in packaged food, soft drinks, biocides, dentifrices, etc. Health effects in children exposed to tin and tin compounds have not been investigated yet. Therefore, we evaluated the possible teratogenic effects and genotoxic of SnCl(2) in zebrafish (Danio rerio) adults and their embryos. In the embryo-larval study, SnCl(2) showed embryo toxicity and developmental delay after exposure to the various concentrations of 10-250 μM for 120 h. Teratogenic effects including morphological malformations of the embryos and larvae were observed. The embryos exposed to 100 μM displayed tail deformation at 28 hpf and the larvae exposed to 50 μM showed reduced body growth, smaller head and eyes, bent trunk, mild pericardial edema, and smaller caudal fin at 96 hpf. The results of the teratological study show that SnCl(2) induced a significant decrease in the number of living embryos and larvae. Regarding the chromosome analysis, SnCl(2) induced a dose-dependent increase in the micronucleus (MN) frequency in peripheral erythrocytes of adult zebrafish. In blood cells, the 25 μM dose of SnCl(2) caused a nonsignificant increase in the total chromosomal aberrations, but the high doses significantly increased the total number of chromosomal aberrations compared with the control groups. Overall, the results clearly indicate that SnCl(2) is teratogenic and genotoxic to zebrafish.

Genetic and epigenetic characteristics of human multiple hepatocellular carcinoma

BackgroundMultiple carcinogenesis is one of the major characteristics of human hepatocellular carcinoma (HCC). The history of multiple tumors, that is, whether they derive from a common precancerous or cancerous ancestor or individually from hepatocytes, is a major clinical issue. Multiple HCC is clinically classified as either intratumor metastasis (IM) or multicentric carcinogenesis (MC). Molecular markers that differentiate IM and MC are of interest to clinical practitioners because the clinical diagnoses of IM and MC often lead to different therapies.MethodsWe analyzed 30 multiple tumors from 15 patients for somatic mutations of cancer-related genes, chromosomal aberrations, and promoter methylation of tumor suppressor genes using techniques such as high-resolution melting, array-comparative genomic hybridization (CGH), and quantitative methylation-specific PCR.ResultsSomatic mutations were found in TP53 and CTNNB1 but not in CDKN2A or KRAS. Tumors from the same patient did not share the same mutations. Array-CGH analysis revealed variations in the number of chromosomal aberrations, and the detection of common aberrations in tumors from the same patient was found to depend on the total number of chromosomal aberrations. A promoter methylation analysis of genes revealed dense methylation in HCC but not in the adjacent non-tumor tissue. The correlation coefficients (r) of methylation patterns between tumors from the same patient were more similar than those between tumors from different patients. In total, 47% of tumor samples from the same patients had an r ≥ 0.8, whereas, in contrast, only 18% of tumor samples from different patients had an r ≥ 0.8 (p = 0.01). All IM cases were highly similar; that is, r ≥ 0.8 (p = 0.025).ConclusionsThe overall scarcity of common somatic mutations and chromosomal aberrations suggests that biological IM is likely to be rare. Tumors from the same patient had a methylation pattern that was more similar than those from different patients. As all clinical IM cases exhibited high similarity, the methylation pattern may be applicable to support the clinical diagnosis of IM and MC.

Evaluation of cytotoxicity and genotoxicity of Inula viscosa leaf extracts with Allium test.

I. viscosa has been used for years in folk medicine for its anti-inflammatory, antipyretic, antiseptic, and paper antiphlogistic activities. In this study, cytotoxic and genotoxic effects of I. viscosa leaf extracts on the root meristem cells of Allium cepa have been examined. Onion bulbs were exposed to 2.5 mg/ml, 5 mg/ml, and 10 mg/ml concentrations of the extracts for macroscopic and microscopic analysis. Tap water has been used as a negative control and Ethyl methanesulfonate (EMS) (2 · 10−2 M) has been used as a positive control. The test concentrations have been determined according to doses which are recommended for use in alternative medicine. There has been statistically significant (P < .05) inhibition of root growth depending on concentration by the extracts when compared with the control groups. All the tested extracts have been observed to have cytotoxic effects on cell division in A. cepa. I. viscosa leaf extract induces the total number of chromosomal aberrations and micronuclei (MNC) formations in A. cepa root tip cells significantly when compared with control groups. Also, this paper shows for the first time the induction of cell death, ghost cells, cells with membrane damage, and binucleated cells by extract treatment. These results suggest the cytotoxic and genotoxic effects of the I. viscosa leaf extracts on A. cepa.

Anticlastogenic effect of caffeic acid phenethyl ester on cisplatin-induced chromosome aberrations in rat bone marrow cells

Caffeic acid phenethyl ester (CAPE) is an antioxidant that can scavenge free radicals and protect cellular macromolecules, including DNA and proteins, from oxidative damage induced by various agents. The protective effect of CAPE on cisplatin-induced chromosome aberrations has been determined in rat bone marrow cells. The animals were pretreated with a single dose of CAPE (10 micromol/kg body weight [b.w.]) injected intraperitoneally (i.p.) 24 hours before the administration of cisplatin and then sacrificed 24 hours after the cisplatin administration. Cisplatin was administered to rats either alone (5 mg/kg b.w., i.p.) or after CAPE treatment. CAPE has led to a statistically significant decrease in the total number of chromosomal aberrations and abnormal metaphases induced by cisplatin when compared with only cisplatin given groups. We have concluded that CAPE could prevent cisplatin-induced chromosome aberrations by establishing a potent free radical scavenger effect.

Effect of Every-Other-Day Fasting on Spontaneous Chromosomal Damage in Rat's Bone-Marrow Cells

Dietary restriction in experimental rodents, either by calorie restriction (CR) or by every-other-day fasting (EODF), was shown to protect against cancer and increase lifespan. One of the suggested hypotheses to explain the beneficial effects of dietary restriction is that the diet stabilizes the integrity of the genetic information. The effects of EODF on the spontaneous frequency of sister chromatid exchanges (SCE) and chromosomal aberrations (CA) were examined in bone-marrow cells of 3-mo-old Wistar male rats. After 12 wk of EODF diet, significant reduction in the frequency of SCE and total number of CA was observed. Data indicate a protective effect of EODF diet against spontaneous mutations in rats.

DNA copy number alterations correlate with survival of esophageal adenocarcinoma patients

Despite recent advances in surgical and multidisciplinary treatment, prognosis for patients with esophageal adenocarcinoma remains poor, and the low prognostic significance of pTNM staging suggests that additional parameters are needed. To identify genomic abnormalities characteristic of esophageal adenocarcinoma, a panel of 33 samples obtained at surgery from previously untreated patients were analyzed by muliplex ligation-dependent probe amplification technique. We detected frequent gains of 6p, 8q, 13q, 17q, 20q, and losses of 4q, 5q, 15q, and 18q. When DNA copy number changes were correlated to clinicopathological features of patients no association was found between the number of chromosomal aberrations and gender, age, tumor grade or pTNM staging. However, interestingly, a significant correlation between patient survival and total number of chromosomal aberrations was found when esophageal adenocarcinoma cases were stratified according to the median of survival (20 months) (P=0.002) or the median of aberrations (12 aberrations) (P=0.014). Evaluation of the distribution of gains and losses at the level of single chromosomes indicated that gains on chromosomes 5, 6, 8, 11, 20 and losses on chromosomes 1, 3, 5, 11, and 18 were significantly different in the two survival groups. Furthermore, when single gene imbalances were analyzed in further details, we found that besides alterations that involve genes shared by both survival groups, a few genes (KIAA0170, EMS1, ABCC4, F3, and MIF) were altered only in samples from patients with poor survival. Thus, we established a good correlation between the total number of chromosomal alterations and survival, suggesting that the estimation of total imbalances might represent an additional indicator of disease outcome. In addition, the finding of alterations specific for the more aggressive esophageal adenocarcinoma subset might represent promising biomarkers to increase the accuracy of clinical outcome prediction.

Developmental and genetic toxicity of stannous chloride in mouse dams and fetuses

Humans are exposed to stannous chloride (SnCl 2) present in packaged food, soft drinks, biocides, dentifrices, etc. Health effects in children exposed to tin and tin compounds have not been investigated yet. Therefore, we evaluated the possible teratogenic and genotoxic effects of SnCl 2 in pregnant female mice and their fetuses. Teratogenic effects including morphological malformation of the fetus and its skeleton were observed. Exposures to environmental stressors including toxic chemicals that have the potential of modulating the immune system can often be linked to ecologically relevant endpoints, such as reduced resistance to disease. Therefore, the semi-quantitative reverse-transcription PCR (RT-PCR) assay was used to evaluate the expression of immune-response genes in the liver of SnCl 2-treated dams and their fetuses. Bone-marrow cells of dams and fetuses were investigated for the presence of aberrant chromosomes. Three oral doses of SnCl 2 (2, 10 and 20 mg/kg bw) were tested. The results of the teratological study show that SnCl 2 induced a significant decrease in the number of living fetuses and a significant increase in the number of post-implantation losses. The high dose of SnCl 2 induced complete post-implantation loss. Furthermore, SnCl 2 caused reduction in the ossification of the fetal skeleton. The RT-PCR assay showed that the immune-response genes GARP and SIMP were not expressed in the liver of dams and fetuses in the controls or in the group treated with SnCl 2 at 2 mg/kg bw. However, the expression of these genes was up-regulated in the groups treated with the other doses of SnCl 2. Regarding the chromosome analysis, SnCl 2 induced a dose-dependent increase in the frequency of individual and total chromosomal aberrations ( P ≤ 0.01) in bone-marrow cells of dams. In fetal cells, the 2-mg/kg bw dose of SnCl 2 caused a non-significant increase in the total chromosomal aberrations, but the 10-mg/kg bw dose significantly increased the total number of chromosomal aberrations ( P ≤ 0.01) compared with the control group.

Acetylsalicylic acid exhibits anticlastogenic effects on cultured human lymphocytes exposed to doxorubicin

Acetylsalicylic acid (ASA) is a non-steroidal anti-inflammatory drug (NSAID) with many pharmacological properties, such as anti-inflammatory, antipyretic and analgesic. Many studies have suggested the possible efficiency of ASA and other NSAIDs in preventing cancer. ASA could also have antimutagenic and antioxidant properties. The aim of this study was to investigate the possible clastogenic and anticlastogenic effects of different concentrations of ASA on doxorubicin-induced chromosomal aberrations in human lymphocytes. Human blood samples were obtained from six healthy, non-smoking volunteers; and the chromosomal aberration assay was carried out using conventional techniques. The parameters analyzed were mitotic index, total number of chromosomal aberrations and percentage of aberrant metaphases. The concentrations of ASA (25, 50 or 100 μg/mL) tested in combination with DXR (0.2 μg/mL) were established on the basis of the results of the mitotic index. The treatment with ASA alone was neither cytotoxic nor clastogenic ( p > 0.01). In lymphocyte cultures treated with different combinations of ASA and DXR, a significant decrease in the total number of chromosome aberrations was observed compared with DXR alone ( p < 0.01). This protective effect of ASA on DXR-induced chromosomal damage was obtained for all combinations, and it was most evident when ASA was at 25.0 μg/mL. In our experiments, ASA may have acted as an antioxidant and inhibited the chromosomal damage induced by the free radicals generated by DXR. The identification of compounds that could counteract the free radicals produced by doxorubicin could be of possible benefits against the potential harmful effects of anthracyclines. The results of this study show that there is a relevant need for more investigations in order to elucidate the mechanisms underlying the anticlastogenic effect of ASA.

Evaluation of DNA damage in white blood cells of healthy human volunteers using the alkaline comet assay and the chromosome aberration test.

The present study was undertaken to contribute to the characterization of the degree of variability in baseline damage in white blood cells from control population, and to investigate how this variability is associated with external and internal factors. Altogether 170 healthy volunteers, randomly selected from the general population of the Republic of Croatia, participated in the study. Two sensitive tests: the alkaline comet assay and the chromosome aberration test were applied to study the background levels of DNA damage in their white blood cells. The results point to inter-individual differences, indicating different genome sensitivity. As revealed by both assays, the background levels of DNA damage were mostly influenced by smoking habit as well as medical exposure (especially to diagnostic X-rays). Sex and age of subjects did not significantly influence the values of DNA damage recorded in the white blood cells. Although higher levels of DNA damage were recorded in blood samples collected during winter and autumn, they were mostly influenced by medicinal exposure and smoking habit. Statistical evaluation of the data confirmed that a positive correlation exists between DNA migration and the number of long-tailed nuclei found with the comet assay and the total number of chromosome aberrations. The data obtained can serve as control values in forthcoming biomonitoring studies.