Micronucleus Frequency In Peripheral Blood Lymphocytes Research Articles

Artemisia vulgaris L., Artemisia alba Turra and their constituents reduce mitomycin C-induced genomic instability in human peripheral blood lymphocytes in vitro

This study aimed to evaluate the effect of aqueous and acetone extracts from Artemisia vulgaris L. (AV) and Artemisia alba Turra (AA), and two major polyphenols compounds (3,5-dihydroxybenzoic acid and quercetin-3-O-glucopyranoside) presented in both extracts of the plants against mitomycin C (MMC)-induced genomic instability. Genomic instability was measured using cytokinesis block micronucleus (MN) assay in human peripheral blood lymphocytes (PBLs) in vitro by analyzing two biomarkers – MN and nuclear division index (NDI). Extracts were tested in a concentration-dependent manner (10–250 µg/mL), while 3,5-dihydroxybenzoic acid and quercetin-3-O-glucopyranoside were tested in three different concentrations, in combination with 0.5 µg/mL of MMC. Aqueous and acetone extracts obtained from both plants significantly reduced MMC-induced MN frequency in PBLs, compared to positive control cells (p < 0.05). Extracts from AV did not affect NDI, whereas the concentrations of 10–100 μg/mL of aqueous and acetone AA extracts significantly elevated MMC-decreased NDI values in comparison to positive control cells (p < 0.05). Combined treatment of 3,5-dihydroxybenzoic acid and MMC showed a significant reduction of MMC-induced MN frequency, while quercetin-3-O-glucopyranoside increased MN frequency compared to positive control cells (p < 0.05). Both compounds decreased NDI values but only at the highest tested concentration of quercetin-3-O-glucopyranoside it was of greater significance. In conclusion, all extracts from AV and AA and 3,5-dihydroxybenzoic acid showed protective effect, whereby aqueous AA demonstrated the highest protective effect on MMC- induced genomic instability, while quercetin-3-O-glucopyranoside showed co-mutagen effect.

Effect of systemic treatment on the micronuclei frequency in the peripheral blood of patients with metastatic colorectal cancer.

Colorectal cancer (CRC) is the third most diagnosed type of cancer affecting males, and the second most diagnosed type of cancer affecting females, and one of the leading causes of cancer-related mortality globally. The estimation of the micronuclei (MN) frequency in peripheral blood lymphocytes (PBLs) from patients with CRC is proposed as a prognostic/predictive easy-to-use biomarker. In this study, we aimed to investigate the effects of systemic treatment on the MN frequency in PBLs from patients with CRC in order to determine the effectiveness of the MN frequency as a biomarker. For this purpose, from 2016 to 2018, we quantified the MN frequency as a prognostic/predictive biomarker in serial samples from 25 patients with metastatic CRC (mCRC) using cytokinesis block micronucleus assay (CBMN assay). The MN frequency in the PBLs of the patients was evaluated before, during the middle and at the end of the therapy (approximately 0, 3 and 6 months). The results revealed a common pattern regarding the fluctuation in the MN frequency. Statistical analysis confirmed that when the disease response was estimated with radiological criteria, a good response was depicted at the MN frequency and vice versa. Consequently, the findings of this study suggest that the MN frequency may serve as a promising prognostic/predictive biomarker for the monitoring of the treatment response of patients with CRC.

Micronuclei frequency in peripheral blood lymphocytes and levels of anti-p53 autoantibodies in serum of residents of Kowary city regions (Poland) with elevated indoor concentrations of radon

IntroductionNinety four residents of Kowary city (Poland) have been investigated for environmental radon exposure that ranged from 0.24 WLM to 9.6 WLM (activity concentration range: 35–2700 Bq/m3). Kowary was chosen because of uranium mineralisation in its close vicinity. MethodWhole population studied was divided into two groups: exposed to low radon activity concentrations resulting in the exposure of ≤0.55 WLM (value corresponding to the exposure to 100 Bq/m3 during whole year), and exposed to high radon activity concentration (>0.55 WLM). In the two groups two selected biomarkers in blood were assessed: the cytokinesis-block micronucleus assay (CBMN) on peripheral blood lymphocytes (PBL), and the levels of anti-p53 antibodies in serum measured because some data indicate increased expression of the antibodies in individuals after exposure to DNA damaging agents including radon. The potential confounding factors known to influence micronuclei (MN) frequency were also measured in serum: vitamin B12, folic acid, as well as total calcium. ResultsIn the present study no significant correlation was found between MN frequency in PBL and radon exposure. Among all persons investigated only 11 had detectable levels of the anti-p53 antibodies, whereas only 3 persons had positive result. Therefore, the group was too small to perform any meaningful statistical analysis and to conclude on any association. Cigarette smoking did not significantly influence the number of MN. There was a significant positive correlation observed between MN frequency and age, as well as higher MN frequency was detected in women. ConclusionThe problem of the radon exposure is still unresolved and needs further studies on bigger human cohorts in order to search for more sensitive biomarkers.

Hair straightening products and the risk of occupational formaldehyde exposure in hairstylists

Hair straitening products are widely used by hairstylists. Many keratin-based hair smoothing products contain formaldehyde. This study aimed to investigate occupational formaldehyde exposure among hairstylists dealing with hair straightening products and the relation between genotoxicity biomarkers and the short-term formaldehyde exposure concentrations and the working years. The study was carried out in Cairo, Egypt on 60 hairstylists use hair straightening products divided into two groups according to the working years. All hairstylists were subjected to micronucleus (MN) frequencies in both epithelial buccal cells (EBC) and peripheral blood lymphocytes (PBL). Fifteen-minute (min) formaldehyde exposure concentrations were measured at workplace during hair straightening procedure. Fifteen-minute formaldehyde concentrations in both groups exceeded the National Institute for Occupational Safety and Health and the American Conference of Governmental Industrial Hygienist thresholds levels. The MN frequencies in EBC and PBL showed a significant increase in group II in comparison to control and group I, which in turn showed a significant increase in MN frequency in PBL and a nonsignificant increase in the MN frequency in EBC when compared to control. A positive correlation was found between genotoxicity biomarkers and working years. Occupational exposures to hair straightening products in the studied hairstylist were found to expose them to formaldehyde concentrations that exceeded the standard limits. All selected genotoxicity biomarkers showed a significant increase in exposed workers and were positively correlated to the duration of exposure.

Assessment of the association between the frequency of micronucleus and p16INK4a/Ki-67 co-expression in patients with cervical intraepithelial lesions

ABSTRACTHuman papilloma virus (HPV) infection is the main etiological factor for cervical intraepithelial lesions (CIN). An important characteristic of this process is the loss of genome stability. Therefore, it is imperative to use biomarkers of DNA damage caused by genomic instability to identify high risk individuals. We investigated the frequency of micronuclei (MN) in peripheral blood lymphocytes (PBL) of 20 patients, diagnosed as histologically CIN 1 and 10 healthy controls. We also examined the frequency of other nuclear anomalies including nucleoplasmic bridges (NPBs) and nuclear buds (NBUDs) in PBL of patients with CIN 1 and healthy controls, and evaluated the benefits of p16INK4a and Ki-67 (p16INK4a/Ki-67) immunohistochemical double staining for identifying cervical squamous cells that express HPV E6/E7 oncogenes. We analyzed the association between the frequency of MN in PBL and the amount of p16INK4a/Ki-67 co-expression in CIN 1 patients to establish genomic instability. Among CIN 1 subjects, 15% exhibited diffuse p16INK4a/Ki-67 co-expression and were considered high positive, 25% of the CIN 1 cases exhibited p16INK4a/Ki-67 co-expression restricted to the lower part of the epithelium and were considered low positive and the remaining 60% of cases were negative. The frequency of MN, NPBs and NBUDs differed significantly among groups. We found a statistically significant positive correlation between p16INK4a/Ki-67 co-expression and the frequency of MN, NPBs and NBUDs in PBL. Our findings demonstrate the efficacy of p16INK4a/Ki-67 double immunostaining for histological samples with CIN 1. MN frequency in PBL might be useful for detecting genomic instability in cases of HPV infection and CIN.

Hypermethylation of CpG islands is associated with increasing chromosomal damage in chinese lead-exposed workers.

Lead is a widely existing environmental pollutant with potential carcinogenicity. To investigate the association of blood lead level (B-Pb) with potential chromosomal damage and cancer, we analyzed micronucleus (MN) frequency of peripheral blood lymphocytes (PBLs) and the methylation status of six human tumor suppressor genes (TSGs) post lead exposure. In the study, 147 lead-exposed workers were divided into two groups according to their B-Pb P50 value, with other 50 lead-unexposed workers as a control group. The cytokinesis-blocked micronucleus (CBMN) assay was performed to detect chromosomal damage of PBLs of both lead-exposed and -unexposed workers. The methylation-specific polymerase chain reaction (MSP-PCR) was further used to examine the methylation status of six TSGs (GSTP1, hMLH1, MGMT, p14, p15, and p16). Results showed that MN frequencies of high B-Pb workers 8.1 ± 3.1‰ and low B-Pb workers 5.7 ± 2.3‰ were significantly higher than that of control group 2.8 ± 1.9‰ (P < 0.01), while the MN frequency of high B-Pb workers was also higher than that of the low B-Pb workers (P < 0.01). The MN frequency in PBLs of lead-exposed group with the methylated TSGs was significantly higher than that in PBLs with the unmethylated TSGs (P < 0.05). Notably, the CpG island methylator phenotype (CIMP) correlated with chromosome damage (P < 0.05). Additionally, workers with high B-Pb had higher chromosome damage than those with low B-Pb (P < 0.05). Taken altogether, the results suggest that lead-exposed workers with CIMP positive and high B-Pb have a higher risk of being vulnerable to tumorigenesis. Environ. Mol. Mutagen. 59:549-556, 2018. © 2018 Wiley Periodicals, Inc.

Association Between Inherited Thrombophilia in Pregnancy and Micronucleus Frequency in Peripheral Blood Lymphocytes.

The aim of this study was to determine possible predictors of an increased frequency of micronucleus (MN) and the impact of thrombophilia on the chromosomal instability in peripheral blood lymphocytes (PBL) of pregnant women in their first trimester. This study was designed as a case-control study on 74 pregnant women. It was performed in the gestational age of 11 to 14 weeks, when blood samples were collected and incubated for 72 hours. The individual MN frequency in PBL was measured by cytokinesis-block micronucleus (CBMN) assay. Women were grouped in control group [≤4 MN/1000 binucleated (BN) cells] and case group (>4 MN/1000 BN cells). Potential mutagenic effects of exogenous/endogenous factors in pregnant women were analyzed. By analyzing the given results, it can be concluded that pregnant women with thrombophilia have 26.69-times more chance of having a frequency of >4 MN/1000 BN than pregnant women with no thrombophilia. Our research was primarily aimed at showing that the presence of thrombophilia was a statistically important predictor of an increased MN frequency in pregnant women and it can predict about one-third of the total variance in MN frequency in the studied population.

Micronucleus Expression and Acute Leukemia Prognosis

The micronucleus frequency (MNF) in peripheral blood lymphocytes (PBL) is a biomarker of chromosomal damage and genome instability in human populations.The relationship of micronucleus frequency with prognosis of patients with acute leukemia is not clear. We therefore investigated MNF in mitogen-activated peripheral blood lymphocytes from patients with hematologic diseases and solid tumours. Patients included 50 with acute leukemia, 49 diagnosed with myelodysplastic syndrome (MDS), 54 with benign blood diseases, and 45 with solid tumours, examined with 50 healthy controls. The mean MNF was significantly higher in cases of hematologic diseases and solid tumor patients than in healthy controls (P<0.001). There was no evident difference between MNF in the acute leukemia (7.15 ± 2.18) and solid tumor groups (7.11 ± 1.47), but both were higher than in the MDS group (5.12 ± 1.29) and benign blood diseases group (3.08 ± 1.08). Taking 7.15%, the average MNF of the acute leukemia group as standard, and dividing 50 cases of acute leukemia patients into high MNF group (MNF ≥ 7.15%) and low MNF group (MNF<7.15%). The overall response (complete remission + partial remission) rates of the low MNF group were significantly higher than in the high MNF group (P=0.001). The high MNF group further showed lower overall survival rates than the low MNF group. MNF expression and progression-free survival seemed to have a opposite relationship, with a correlation coefficient of -0.702. These data indicate that MNF in peripheral blood lymphocytes is important for evaluation of prognosis of acute leukemia patients, and it can reflect progression of disease to a certain degree.

Comparative study of genotoxicity and antimutagenicity of methanolic extracts from Teucrium chamaedrys and Teucrium montanum in human lymphocytes using micronucleus assay

Since Teucrium chamaedrys and Teucrium montanum are the most popular plants used in the treatment of many diseases, we evaluated genotoxic potential of their methanolic extracts on cultured human peripheral blood lymphocytes (PBLs) using cytokinesis-block micronucleus (MN) assay. Cultures were treated with four concentrations of both plants (125, 250, 500 and 1,000μg/ml), both separately and in combination with mitomycin C (MMC). The results revealed that extract of T. chamaedrys administered at the tested concentrations did not significantly affect the mean MN frequency in comparison to untreated cells. Methanolic extract of T. montanum increased the mean MN frequency in PBL at the tested concentrations, but significantly only at the concentration of 1,000μg/ml. In all tested concentrations, the extract of T. chamaedrys significantly reduced the MMC-induced MN frequency, in a dose dependent manner (r=-0.687, p<0.01). The extract of T. montanum decreased the MMC-induced MN frequency at the tested concentrations, but statistically only at 125μg/ml. Both extracts administered alone did not significantly affect the nuclear division index (NDI) at the tested concentrations. In the combined treatments with MMC, the extract obtained from T. chamaedrys in the concentrations of 500 and 1,000μg/ml significantly decreased NDI values in comparison to MMC-treated cells alone, while the extract of T. montanum significantly decreased NDI at all tested concentrations. Both extracts nonsignificantly decreased NDI at all tested concentrations in comparison to untreated cells. Our results suggest the important function of T. chamaedrys extract in cancer therapy, this methanolic extract may prevent genotoxic effects of chemotherapy in PBLs.

Correlation between Micronuclei Frequency in Peripheral Blood Lymphocytes and Retention of 131-I in Thyroid Cancer Patients

Differentiated thyroid cancers (DTCs) derive from thyroid follicular cells and include papillary and follicular cancers. In patients with DTCs, the initial treatment includes thyroidectomy and radioactive iodine (131-I) therapy. The objective of this study was to examine whether the intensity of DNA damage in peripheral blood lymphocytes (PBLs) of DTC patients depends on the amount of 131-I retained in the selected regions of interest (thyroid and abdominal region) as well as in the whole-body 72 hours after therapy. In addition, the possible influence of other factors that may affect micronuclei (MN) frequency, such as age, gender, smoking habits, and histological type of tumour was analyzed. The study population consisted of 22 DTC patients and 20 healthy donors. Data on the distribution of 131-I were obtained from the whole-body scans. MN frequency and cytokinesis-block proliferation index (CBPI) were measured using cytokinesis-block micronucleus assay. 131-I therapy significantly increased the MN frequency (19.50±6.90 vs. 27.10±19.50 MN) and significantly decreased the CBPI (1.52±0.20 vs. 1.38±0.17) in patients' lymphocytes. There was a clear correlation between the increased MN frequency and 131-I accumulation in the thyroid region in patients without metastases. The MN values did not differ in relation to the factors that could affect MN, such as age, gender, smoking habits, and histological type of tumour. In conclusion, the MN frequency in PBLs of DTC patients without metastases depends on the accumulation of 131-I in the thyroid region and does not depend on the other factors examined.

Inter-individual variance in micronuclei frequency in lymphocytes of patients with cervical insufficiency

The aim of this work was to explain the inter-individual variance in baseline and induced micronuclei (MN) frequency in peripheral blood lymphocytes (PBLs) of females with uterine cervical insufficiency. The baseline and induced MN response of the PBLs in 32 patients were investigated using the cytokinesis-block micronucleus (CBMN) method. The obtained mean values of induced MN frequency (11.31 ? 4.44/1000 BN cells), were significantly higher (p &lt; 0.001) in comparison to their baseline MN frequencies (7.81 ? 3.33 MN/1000 BN cells). The analysis of variance (ANOVA) showed statistically significant difference between-group vs. within-group variance in baseline (p &lt; 0.05) and induced MN frequency (p &lt; 0.001), in professionally exposed patients when compared to the non-exposed. Multivariate logistic regression analysis confirmed that patients with high baseline MN frequency (cut-off 8.5 MN/1000 MN), had significantly increased (odds ratio OR = 5.875; CI = 1.28 - 26.795, p &lt; 0.05) induced MN frequency (&gt;12 MN/1000 BN cells). Our results suggest that the baseline MN frequency in PBLs directly influences the scope of the induced MN response.

Chromosomal instability in peripheral blood lymphocytes of patients with reproductive failure assessed by micronucleus assay

We investigated chromosomal instability in peripheral blood lymphocytes (PBL) of patients with reproductive failure in respect to age, smoking habits, gender, miscarriages, and semen parameters. The study involved 36 individual cases of reproductive failure (18 men and 18 women) attended at the Clinical Centre of Kragujevac, Serbia, and 30 healthy subjects (15 men and 15 women). Micronuclei (MN) frequency was estimated in PBL using the cytokinesis-block micronucleus (CBMN) assay. The baseline MN frequencies were significantly higher (p=0.031; p<0.001) in male [(9.22 ± 4.70) MN per 1000 BN cells] and female patients [(13.50 ± 2.5) MN per 1000 BN cells] than in male and female healthy controls [(6.27 ± 2.66) MN per 1000 BN cells; (6.80 ± 2.98) MN per 1000 BN cells]. The mean baseline MN frequency did not significantly differ between miscarriage groups and between patients with and without normal values of semen parameters. The correlations between poor sperm concentration (<20x106 mL-1), rapid progressive motility (<25 %), normal morphology (<30 %), and MN frequencies were negative, but not statistically significant. We found that only gender significantly influenced the MN rates in analysed patients. There were no significant differences between age groups and between smokers and non-smokers in patients and control samples. We conclude that the increase in baseline MN frequency in PBL of patients with reproductive failure corresponds to the increase in chromosomal damage, which occurs as a result of complex events that cause reproductive disorders.

Cervical precancerous lesions – chromosomal instability in peripheral blood lymphocytes in relation to lesion stage, age and smoking habits

To evaluate chromosomal damage in peripheral blood lymphocytes (PBL) of patients newly diagnosed with cervical precancerous lesions with respect to age, smoking habits, miscarriages, abortions and lesion stage. Clinical study. Clinic of Gynecology and Obstetrics in Kragujevac, Serbia, during 2009-2010. The analyzed samples included 41 untreated patients aged 24-65 years with a diagnosed low-grade squamous intraepithelial lesion (LSIL; 19 patients) or a high-grade squamous intraepithelial lesion (HSIL; 22 patients). Control samples were obtained from 40 healthy women aged 24-53 years. The frequency of micronuclei (MN) was estimated in circulating lymphocytes by using the cytokinesis-block micronucleus assay. The frequency of MN in PBL. The mean MN frequencies of both LSIL and HSIL patients were significantly higher than the MN frequency of healthy control women. There was no significant difference in MN frequency between LSIL and HSIL patients, between smokers and nonsmokers in both patient and control samples, or between miscarriage groups and abortion groups of patients. Considering confounder factors, age and health status influenced MN frequency. The results suggest that MN frequency in PBL of patients with cervical precancerous lesions corresponds to an increase of chromosomal damage, irrespective of smoking habits, miscarriages, abortions and lesion stages.

The effect of age, gender, diet and lifestyle on DNA damage measured using micronucleus frequency in human peripheral blood lymphocytes

Micronucleus (MN) frequency in cytokinesis-blocked peripheral blood lymphocytes (PBL) has become one of the best-established biomarkers for studying DNA damage occurring in vivo in humans. The application of this method in population biomonitoring studies requires a deep understanding of how lifestyle and common host variables may influence MN frequency in PBL. In this mini-review, an update is provided on results from studies reporting on the impact of age, gender, diet and lifestyle factors (e.g. exercise, alcohol, smoking and recreational drugs) on this biomarker. Evidence from these studies shows that each of these factors, either in isolation or in combination, can significantly influence MN frequency. Proper control for these factors is required to enable better measurement of the impact of other conditions, such as environmental exposure to genotoxins or a susceptible genetic background, on MN frequency in PBL.

Genotoxicity in Filling Station Attendants Exposed to Petroleum Hydrocarbons

Biomonitoring of exposure in workplaces has gained importance in evaluation of human health hazards. Since occupational exposure to petroleum hydrocarbons may have deleterious effects, genotoxicity risk among 200 fuel filling station attendants (FFSAs) and 200 matched controls was investigated. The probable genetic damage was determined by comet assay and micronucleus test in peripheral blood lymphocytes (PBL) of study subjects. Air and blood sample analysis was done to estimate the benzene, toluene, and xylene (BTX) concentrations using gas chromatography-mass spectrometry. The effect of exposure on antioxidant enzymes was also studied by determining the levels of superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), and rate of lipid peroxidation measured as concentration of malondialdehyde (MDA) formed. The results of the present study suggest that there was a statistically significant increase in mean comet tail length (25.09 versus 10.27 μm) and frequency of micronuclei in PBL (11.83 versus 5.83 per thousand; P < 0.05) of FFSAs as compared to controls. BTX concentrations were found to be significantly higher in ambient air of petrol pumps and FFSAs showed elevated levels of these compounds in their breathing zone in comparison to controls (P < 0.05). Blood BTX levels were found to be significantly enhanced in FFSAs. SOD and GPx were significantly decreased with an increased rate of CAT and MDA in FFSAs as compared to controls. The results of our study suggest that exposure to BTX has the potential to cause genetic changes in the exposed subjects. The data highlight the need to maintain safety measures and intervention to minimize exposure.

Reduction of the genomic damage level in haemodialysis patients by folic acid and vitamin B12 supplementation

Cancer incidence and genomic damage of peripheral lymphocytes are elevated in patients with end-stage renal failure. Among other uraemic toxins, homocysteine (Hcy) levels are increased in most of these patients. In healthy individuals, plasma Hcy correlates with the degree of genomic damage observed in peripheral blood lymphocytes (PBL). The accumulation of Hcy can be reduced by supplementation with folic acid and vitamin B12. The aim of this study was to analyse whether this supplementation can also lower the genomic damage in PBL of haemodialysis patients. This may ultimately help to reduce cancer incidence in renal patients. In a prospective study with 27 patients, we analysed the genomic damage in dialysis patients before and at different time points after the initiation of folate/vitamin B12 supplementation. Genomic damage was measured by the frequency of micronuclei, a subset of chromosomal aberrations, in PBL. Supplementation with folic acid and vitamin B12 (more markedly with both) reduced the micronucleus frequency in PBL of dialysis patients. This was not mediated by altered lymphocyte proliferation capacity or changes in DNA cytosine-methylation. Plasma-Hcy was lowered more efficiently by the combined folic acid/vitamin B12 supplementation, and lymphocyte DNA of this group exhibited a nonsignificant trend for a reduction of 1,N(6)-etheno-2'-deoxyadenosine, a marker for oxidative stress. A reduction of the genomic damage in PBL can be achieved in dialysis patients by supplementation with folic acid and vitamin B12. This may be mediated by Hcy reduction.

An increased micronucleus frequency in peripheral blood lymphocytes predicts the risk of cancer in humans

The frequency of micronuclei (MN) in peripheral blood lymphocytes (PBL) is extensively used as a biomarker of chromosomal damage and genome stability in human populations. Much theoretical evidence has been accumulated supporting the causal role of MN induction in cancer development, although prospective cohort studies are needed to validate MN as a cancer risk biomarker. A total of 6718 subjects from of 10 countries, screened in 20 laboratories for MN frequency between 1980 and 2002 in ad hoc studies or routine cytogenetic surveillance, were selected from the database of the HUman MicroNucleus (HUMN) international collaborative project and followed up for cancer incidence or mortality. To standardize for the inter-laboratory variability subjects were classified according to the percentiles of MN distribution within each laboratory as low, medium or high frequency. A significant increase of all cancers incidence was found for subjects in the groups with medium (RR=1.84; 95% CI: 1.28-2.66) and high MN frequency (RR=1.53; 1.04-2.25). The same groups also showed a decreased cancer-free survival, i.e. P=0.001 and P=0.025, respectively. This association was present in all national cohorts and for all major cancer sites, especially urogenital (RR=2.80; 1.17-6.73) and gastro-intestinal cancers (RR=1.74; 1.01-4.71). The results from the present study provide preliminary evidence that MN frequency in PBL is a predictive biomarker of cancer risk within a population of healthy subjects. The current wide-spread use of the MN assay provides a valuable opportunity to apply this assay in the planning and validation of cancer surveillance and prevention programs.

A Molecular Epidemiology Case Control Study on Pleural Malignant Mesothelioma

Pleural malignant mesothelioma is an uncommon neoplasm usually associated with asbestos exposure. The increasing incidence of malignant mesothelioma cases involving individuals with low levels of asbestos exposure suggests a complex carcinogenetic process with the involvement of other cofactors. Cytogenetic studies revealed the complexity of the genetic changes involved in this neoplasm reflecting the accumulation of genomic damage. One of the most used methodologies for assessing genomic damage is the cytokinesis-blocked micronucleus test applied in peripheral blood lymphocytes (PBL). This approach allows the detection of chromosomal alterations expressed in binucleated cells after nuclear division in vitro. This marker could provide a tool for assessing genetically determined constitutional differences in chromosomal instability. A biomonitoring study was carried out to evaluate the micronuclei frequency in PBLs of patients with pleural malignant mesothelioma with respect to lung cancer, healthy, and risk controls as a marker of cancer susceptibility in correlation with the presence of SV40. A significant increased micronuclei frequency was observed in patients with malignant mesothelioma in comparison with all the other groups, the mean micronuclei frequency was double in patients with malignant mesothelioma compared with healthy controls, risk controls, and patients with lung adenocarcinoma (median 11.4 binucleated cells with micronuclei/1,000 binucleated cells versus 6.2, 6.1, and 5.1, respectively). Our data indicate that human T lymphocyte samples carry DNA sequences coding for SV40 large T antigen at low prevalence, both in cancer cases and controls. Evidence of cytogenetic damage revealed as micronuclei frequency in mesothelioma cancer patients could be related to exogenous and endogenous cofactors besides asbestos exposure.

Effect of garlic on micronuclei frequency in peripheral blood lymphocytes of rats with N-methyl-N'nitro-N-nitrosoguanidine-induced gastric carcinoma and precancerous lesions.

To investigate the effects of garlic on micronuclei frequency (MNF) in peripheral blood lymphocytes (PBLs) of Wistar rats with N-methyl-N'nitro-N-nitrosoguanidine (MNNG)-induced gastric carcinoma (GC) and precancerous lesions (PLs). Wistar rats were exposed to MNNG at 1.25 mg/5 mL per day for 10 mo to induce GC and PLs (MNNG group, n = 30); rats not exposed to MNNG served as unmodeled controls (control group, n = 16). The MNNG rats were randomly divided into a prevention treatment group (n = 30; receiving 10 mL of a 10% garlic solution per day) and an untreated model control group (n = 20; receiving tap water). MNF in PBLs were detected at experiment months 10 and 16 mo by the microculture technique. The MNNG group had similar MNF levels at months 10 and 16. Compared to the control group, the MNNG, prevention and untreated model control groups had remarkably higher MNF levels (P < 0.01). The level of PLs was significantly lower in the prevention treatment group than in the untreated model control group (P < 0.01). The prevention group showed significantly lower MNF than the MNNG group (P < 0.01), and the MNF level was reduced in month 16 compared to month 10 (P < 0.01). However, the difference in MNF levels in groups given prevention or treatment was not significant. MNNG exposure exerted continuous mutagenicity and carcinogenicity properties on PBLs, and garlic exerted a remarkable anti-mutagenic and anti-carcinogenic effect. MNF in PBL may be a novel marker of early-stage GC.