A case-control study on asthma and obese patients: Influence of lifestyle patterns, serum trace elements, heavy metals, and total antioxidants.

Background and aim: Asthma is a chronic airway hyperresponsiveness disorder and Obese people have greater rates of asthma incidence and prevalence. Obesity, a complex condition, can cause nutritional metabolic problems that change trace elements and minerals. Trace element and antioxidant levels affect asthma aetiology. In this study, we aim to determine the serum levels of trace elements Zn, Fe, Cu, Mg, Co, Ni, Pb, Cd, and Cr, total antioxidants (TAS), and lifestyle that determine specific clinical conditions in asthma and obesity patients from Vellore City (Tamil Nadu, India). Methods: A case-control study to determine the level of the serum trace elements with 838 subjects (n = 242 asthma patients, n = 140 asthmatic obese, n = 185 obese patients, and n = 271 controls) between the ages of 20 and 60 years was carried out. Asthma was diagnosed based on the clinical examination and pulmonary function tests. Trace element levels were determined by atomic absorption spectrophotometry (AAS) in serum, and a DPPH-free radical scavenging assay was used to determine the total antioxidant capacity level in serum. Result: In asthma male patients, serum levels of Zn, Fe, Cu, Mg, and TAS were significantly lower and Pb, Cd, and Cr significantly higher, whereas in female asthma patients, serum levels of Zn, Fe, Mg, and TAS were significantly lower and Pb significantly higher. In asthmatic obese male patients, Fe, Cu, and TAS were significantly lower, and Pb, Cd, and Co were significantly higher; in asthmatic obese female patients, Zn, Fe, Cu, Mg, and TAS were significantly lower, and Ni was significantly higher. In obese male patients, Zn, Fe, Cu, and TAS were significantly lower and Cd was significantly higher, and in obese female patients, Zn, Fe, Cu, Mg, and TAS were significantly lower. Conclusion: The influence of the level of trace elements, heavy metal, total antioxidant, and the lifestyle patterns, may increase the risk of asthma and obesity.

Role of sex in immune response and epigenetic mechanisms.

The functioning of the human immune system is highly dependent on the sex of the individual, which comes by virtue of sex chromosomes and hormonal differences. Epigenetic mechanisms such as X chromosome inactivation, mosaicism, skewing, and dimorphism in X chromosome genes and Y chromosome regulatory genes create a sex-based variance in the immune response between males and females. This leads to differential susceptibility in immune-related disorders like infections, autoimmunity, and malignancies. Various naturally available immunomodulators are also available which target immune pathways containing X chromosome genes.

Association of polymorphisms of vitamin D gene in children with asthma and allergic rhinitis - Hospital based study.

Vitamin D gene polymorphisms are known to be associated with asthma and allergic rhinitis in children. However, the genetic association of the same in South Indian children with above condition is still unknown. The present study was designed with the objective to analyze the association of polymorphisms of vitamin D receptor gene (VDR) (rs797532, rs154410, rs2258470, rs731236) and transport gene of vitamin D (rs7041) in children with asthma and allergic rhinitis in South India. Children (1-18years) presenting with symptoms suggestive of asthma and allergic rhinitis to hospital based outpatient department, in Vellore, South India were recruited as cases and children presenting with minor illness without respiratory complaints were enrolled as controls during January 2018 to September 2021. Polymorphisms were genotyped using tetra-arms PCR. Significant increase in levels of absolute eosinophil counts and serum IgE levels with decrease in vitamin D levels was seen among the cases. Significant association between levels of vitamin D and serum IgE was also observed. Analysis of polymorphisms showed that, in comparison to homozygous major allele the odds of having heterozygous (OR0.55 (0.3, 0.99) and homozygous minor form (OR0.52 (0.28, 0.97) of rs7975232, homozygous minor (OR 0.51 (0.34, 0.76)) and alternate allele (OR 0.7 (0.53, 0.93)) of rs154410 and homozygous minor form (OR 0.57 (0.37, 0.88) of rs731236 was significantly lesser among the cases. Genotypic model of rs154410 (p0.023) and allele form of rs7041 (p 0.041) were significantly associated with vitamin D levels however no association of gene blocks with cases was seen in haplotype analysis. There was an apparent gene pool difference noted in comparative analysis between Indian studies. The study is the first in south India to analyze levels of serum IgE, Vitamin D levels, association of VDR polymorphisms, and rs7041 in children with asthma.

Taste receptors influencing effective modalities in human health - A cutting edge update on TAS1R and TAS2R receptor polymorphisms in taste perception and disease risk.

Background: Taste is the characteristic sensory modality of the gustatory system associated with dietary intake. The ability of humans to perceive different tastes is predisposed by the activity of taste receptors. The expression of TAS1R family of genes enables the detection of sweetness and umaminess, whereas TAS2R enables the detection of bitterness. The varying levels of expression of these genes within different organs of the gastro-intestinal tract, regulates the metabolism of biomolecules including carbohydrates and proteins. Variations in the gene encoding for taste receptors might affect its binding affinity to tastant molecules and thereby pertain to varying degrees of sensation to taste among individuals. Aim: The goal of this review is to highlight the significant role of TAS1R and TAS2R as a potential biomarker to identify the incidence of morbidities and its probable onset. Method: We thoroughly investigated the SCOPUS, PubMed, Web of Science and Google Scholar databases for literature relating to the association between TAS1R and TAS2R receptors in highlighting the genetic variation during various health morbidities. Results: It has been shown that the abnormalities in taste perception restrain an individual from consuming the adequate amount of food. Taste receptors not only influence the dietary habits but also determine different aspects of human health and well-being. Conclusion: According to the available evidence the dietary molecules conferring varying taste modalities are observed to have therapeutic significance apart from its nutritive value. The taste associated incongruous dietary pattern is a risk factor for various morbidities including obesity, depression, hyperglyceridaemia, and cancers.

Association of telomere length with diabetes mellitus and idiopathic dilated cardiomyopathy in a South Indian population: A pilot study.

Telomere shortening has been associated with ageing and with many age-related diseases including cancer, coronary artery disease, heart failure and diabetes. We sought to investigate the link between telomere shortening and age-related diseases like type 2 diabetes mellitus (DM) (without any complications: DM; with neuropathic complication: DN) and idiopathic dilated cardiomyopathy (IDCM) in south Indian population. We compared telomere lengths of blood lymphocytes taken from patients with associated age-related diseases, namely DM (n = 47), DN (n = 52) and IDCM (n = 34) and controls (n = 46). In addition, we evaluated the relationship between echocardiographic left ventricular ejection fraction (LVEF), left ventricular end diastolic and systolic diameters (LVEDd and LVESd) and telomere length in IDCM patients. Telomere length negatively correlated with age in the cohorts with diabetes and IDCM, and in controls. Average telomere length in diabetes and IDCM patients was significantly shorter than that of controls either before or after adjustments for age and sex. Duration of diabetes in patients with type 2 diabetes did not correlate with telomere length. No correlation was found between the length of telomeres and echocardiography parameters like LVEF, LVEDd and LVESd in IDCM patients. Though echocardiographic characteristics of IDCM did not correlate with telomere length, telomere shortening was found to be accelerated in diabetes (both DM and DN) and IDCM in a south Indian population. Neuropathic complication in diabetes had no effect on telomere shortening. While telomere shortening is a cause or a consequence of diabetic and cardiac pathology remains further investigation, the current study substantiates the usefulness of telomere length measurements as a marker in conjunction with other biochemical markers of age-related diseases.

Oxidative Damage Induced Telomere Mediated Genomic Instability in Cells from Ataxia Telangiectasia Patients.

Our cellular genome is susceptible to cytotoxic lesions which include single strand breaks and double strand breaks among other lesions. Ataxia telangiectasia mutated (ATM) protein was one of the first DNA damage sensor proteins to be discovered as being involved in DNA repair and as well as in telomere maintenance. Telomeres help maintain the stability of our chromosomes by protecting the ends from degradation. Cells from ataxia telangiectasia (AT) patients lack ATM and accumulate chromosomal alterations. AT patients display heightened susceptibility to cancer. In this study, cells from AT patients (called as AT -/- and AT +/- cells) were characterized for genome stability status and it was observed that AT -/- cells show considerable telomere attrition. Furthermore, DNA damage and genomic instability were compared between normal (AT +/+ cells) and AT -/- cells exhibiting increased frequencies of spontaneous DNA damage and genomic instability markers. Both AT -/- and AT +/- cells were sensitive to sodium arsenite (1.5 and 3.0 µg/ml) and ionizing radiation-induced (2 Gy, gamma rays) oxidative stress. Interestingly, telomeric fragments were detected in the comet tails as revealed by comet-fluorescence in situ hybridization analysis, suggestive of telomeric instability in AT -/- cells upon exposure to sodium arsenite or radiation. Besides, there was an increase in the number of chromosome alterations in AT -/- cells following arsenite treatment or irradiation. In addition, complex chromosome aberrations were detected by multicolor fluorescence in situ hybridization in AT -/- cells in comparison to AT +/- and normal cells. Telomere attrition and chromosome alterations were detected even at lower doses of sodium arsenite. Peptide nucleic acid - FISH analysis revealed defective chromosome segregation in cells lacking ATM proteins. The data obtained in this study substantiates the role of ATM in telomere stability under oxidative stress.

Association of vitamin D gene polymorphisms in children with asthma - A systematic review.

INTRODUCTION: The association of Vitamin D and children with asthma is known and there are several individual studies on Vitamin D polymorphisms. However, systematic reviews on all vitamin D associated gene polymorphisms have not been done in children with asthma. OBJECTIVE: To investigate the association of Vitamin D associated gene polymorphisms and asthma in children (0-18 years) by systematic review and meta-analytic approach. METHODS: Our search included 20 full text articles of which 15 were case control studies and 5 used family based linkage disequilibrium method. Total of 2491cases and 3682 controls were included in case control studies, with mean age of 9.58 years and 10.16 years respectively. Quantitative and qualitative analysis were done. RESULTS: Quantitative analysis revealed significant association with protective effect of Apa1 polymorphism in allele (OR 0.81 (0.71,0.91) and homozygous major form (OR 0.83 (0.70,0.98) and Taq 1 minor allele in homozygous form (OR 0.73 (0.58,0.92) in children with asthma. However, the minor allele of Apa1(OR 1.21 (1.07,1.37), Bsm 1 in heterozygous (OR 1.35 (1.07,1.71) and homozygous minor form (OR 1.95 (1.59,2.39), major allele of Fok1(OR1.34 (1.17,1.52) and Taq1 (OR 1.22 (1.08,1.38) were found to be increasing the odds of asthma. Ethnic variations were noted in subgroup analysis. Qualitative analysis of the polymorphisms of the Vitamin D associated metabolic genes also showed significant associations. CONCLUSION: Our review shows significant associations with VDR polymorphisms - Apa1, Bsm1, Fok 1, Taq 1, polymorphisms of Vitamin D metabolic genes - CYP27A1, CYP 2R1, CYP 24A1, GC and genes related to Vitamin D response element (VDRE) in children with asthma. Conducting large studies involving various ethnic regions will strengthen our knowledge on the association and aid in targeted interventions for control of asthma in children.

Delineating the Effects of Ionizing Radiation on Erythropoietic Lineage-Implications for Radiation Biodosimetry.

The overall lethality/morbidity of ionizing radiation exposure involves multiple forms of inhibitory or cytotoxic effects that may manifest in different tissues with a varying dose and time response. One of the major systemic effects leading to lethality of radiation includes its suppressive effect on hematopoiesis, which could be observed even at doses as low as 1-2 Gy, whereas effects on gastrointestinal and nervous systems appear at relatively higher doses in the same order. This article reviews the effects of radiation on the three distinct stages of erythropoiesis-formation of erythroid progenitor cells, differentiation of erythroid precursor cells, and terminal maturation. During these stepwise developmental processes, erythroid progenitor cells undergo rapid expansion to form terminally differentiated red blood cells that are continuously replenished from bone marrow into the circulating peripheral blood stream. Cellular radiation response depends upon many factors such as cell lineage, rate of proliferation, and differentiation status. Therefore, we discuss radiation-induced alterations during the progenitor, precursor, and terminal maturation stages and the implications thereof. Since biomarkers of ionizing radiation exposure in human populations are of great interest for assessing normal tissue injury as well as for biodosimetry in the event of accidental or incidental radiation exposures, we also highlight blood-based biomarkers that have potential utility for medical management.

Assessment of genomic instability and proliferation index in cultured lymphocytes of patients with Down syndrome, congenital anomalies and aplastic anaemia.

One hundred and fifteen cases [Down Syndrome (DS) n = 75, Multiple Congenital Anomalies (MCA) n = 15 and Aplastic Anaemia (AA) n = 25], with respect to their nature of predisposition to cancer, were selected for clinical, cytogenetic and cyto-molecular studies to understand the severity of genomic instability according to the nature of the different diseases. Cytogenetic studies included chromosomal aberration (CA) assays and cytokinesis block micronucleus cytome (CBMN-Cyt) assays. In DS, MCA and AA, average frequencies of nuclear anomalies (NA) were 0.015 ±â€¯0.0006, 0.021 ±â€¯0.00123, 0.031 ±â€¯0.00098, respectively and CA were 0.107 ±â€¯0.003, 0.105 ±â€¯0.008, 0.158 ±â€¯0.006, respectively per metaphase. The extent of genomic instability in patients analysed by CBMN-Cyt assays and CA assays was statistically significant in all groups. Comparatively decreased cytokinesis block proliferation index (CBPI) observed in AA patients of 1.59 ±â€¯0.05, support the assumption that decreased levels of CBPI indicate increased genomic damage. Furthermore, we performed peptide nucleic acid fluorescence in situ hybridisation (PNA FISH) analysis to understand the mechanisms behind genomic instability and telomere dysfunction. PNA FISH showed increased frequencies of telomere signal free ends (0.98 ±â€¯0.13) in individuals with higher genomic instability. Therefore, the results demonstrate that increased chromosomal instability along with higher telomere attrition or loss may initiate gross DNA damage and leads to chromosomal instability, which is an important mechanism for triggering genomic instability - an important hallmark of cancer cells.

Classification of PCR-SSCP bands in T2DM by probabilistic neural network: a reliable tool.

A Probabilistic Neural Network (PNN) is a statistical algorithm and consists of a grouping of multi-class data. The conventional method of detection of DNA mutations by the human eye may not detect the minute variations in PCR-SSCP bands, which may lead to false positive or false negative results. The detection by photographic images may contain a blare (noise) caused during the time of photography; therefore, image processing techniques were used to reduce image noise. PCR-SSCP gels of T2DM patients (n = 100) and controls (n = 100) were initially photographed with equal ratio of pixels and later subjected to a two-stage analysis: feature extraction and PNN. The evaluation of the results was done by quality training and the accuracy was up to 95%, and the human eye analysis showed 80% mutation detection rate. This study proves to be very reliable and gives accurate and fast detection for mutation analysis in diabetes. This method could be extended for analysis in other human diseases.

Evaluation of DNA damage in Type 2 diabetes mellitus patients with and without peripheral neuropathy: A study in South Indian population.

BACKGROUND: The increasing incidence of Type 2 diabetes mellitus globally has collaterally increased the incidence of diabetes-associated complications such as neuropathy. Oxidative stress induced DNA damage is one of the mechanisms implicated in the pathogenesis of diabetic complications. Here we aimed to evaluate the extent of DNA damage in diabetes patients with and without clinical neuropathy using the Cytokinesis Block Micronucleus Cytome assay, in a group of South Indian population. MATERIALS AND METHODS: The Cytokinesis Block Micronucleus Cytome assay was performed in lymphocyte cultures of 42 type 2 diabetes patients (22 with neuropathy and 20 without neuropathy) and 42 age and sex matched controls. Nuclear aberrations like Nuclear Buds, Nucleoplasmic Bridges and Micronuclei were analyzed. RESULTS: The frequency of nuclear aberrations in diabetes patients with neuropathy was higher than compared to diabetes patients without neuropathy. The mean frequencies of nuclear aberrations per cell in diabetes patients with neuropathy and without neuropathy were 0.02 ± 0.02 and 0.01 ± 0.01, respectively. This was significantly higher than in the controls (0.002 ± 0.002) (P < 0.0001). An increasing trend of nuclear aberrations in correlation with the duration of diabetes was observed. CONCLUSION: This study highlights the use of the Cytokinesis Block Micronucleus Cytome assay as a potent tool for the identification of DNA damage, which may prove to be useful biomarker to assess the severity diabetes-associated complications such as neuropathy. Implementation of this technique at the clinical level would potentially enhance the quality of management of patients with diabetes and its complications like neuropathy.

A comparative study of phytohaemagglutinin and extract of Phaseolus vulgaris seeds by characterization and cytogenetics.

Phytohaemagglutinin (PHA) is a lectin obtained from Phaseolus vulgaris (red kidney beans), that acts as a mitogen in human leucocyte culture and is commercially available from Gibco. This PHA (Gibco) was found to be very expensive, hence other inexpensive sources that can be used in all kinds of cytogenetics labs (rich and poor), were attempted. One such successful attempt was PHA extract from seeds of P.vulgaris. This paper details the methodology of extraction and application of PHA from seeds of P.vulgaris. Attempts has been made to identify the chemical and physical properties of the products in the extract, analyzed by various spectroscopic and analytical techniques. The analysis clearly indicates that the product from Phaseolus seeds extract was found to be similar to the commercially available PHA (Gibco) in the cytogenetic study of human leucocyte cultures. The present study enforces the possible utility of the plant extract directly for human leucocyte cultures.

Chromosomal Aberrations and Exon 1 Mutation in the AKR1B1 Gene in Patients with Diabetic Neuropathy.

BACKGROUND: Recent decades have seen an increase in our understanding of a number of pathophysiological processes associated with type 2 diabetes mellitus (DM). Despite increases in understanding and treatment options, diabetic neuropathy remains a significant problem and is associated with tremendous morbidity and mortality. In this regard, oxidative DNA damage is postulated to play a role in diabetes-mediated neuropathic pathogenesis. METHODS: In this pilot investigation, we studied the extent of chromosomal damage utilizing chromosomal aberration (CA) assay in cultured lymphocytes of patients in 3 subgroups: patients with diabetic neuropathy, patients with type 2 DM and no neuropathy, and a control group. RESULTS: The patients with diabetic neuropathy showed a statistically significantly higher rate of CA (P<0.001, 0.086 ± 0.04) compared to the DM patients without neuropathy (0.03 ± 0.02). Samples from subjects with diabetic neuropathy were evaluated to check for mutations in the AKR1B1 gene (exon 1). A significant number of mutations appeared after DNA sequencing within the AKR1B1 gene. Of 50 diabetic neuropathy patient samples analyzed, 10 revealed mutations. CONCLUSION: Our results suggest that painful diabetic neuropathy is a condition with enhanced genomic instability characterized by increased CA and possible mutations. Exon 1 of the gene AKR1B1 showed significant mutations in patients with painful diabetic neuropathy.

Diabetes--increased risk for cancers through chromosomal aberrations?

Diabetes, a comprehensive genetic disease, is principally due to the deregulation of glucose levels in the blood. In addition to contemporary epidemiological studies, systematic substantiation suggests that long-term diabetes leads to cancers due to a variety of reasons. In this study, blood samples were collected with informed consent from confirmed type I diabetic (T1DM, n=25) and type II Diabetic patients (T2DM, n=25) with equal numbers of controls. Further depending on the lifestyle habits they were subdivided into smokers/non-smokers and alcoholics/non-alcoholics. Chromosomal assays were performed for these cases and it was found that there was a significant increase in chromosomal aberration frequency in diabetic patient groups who are exposed to smoking and alcohol than that of normal diabetic groups (T1DM and T2DM). On the other hand, patient groups who were non-smoking and non-alcoholics also showed higher chromosomal aberrations when compared to that of controls. While the mechanisms for these increased chromosomal aberrations in diabetic groups are not clear, they may be due to increased oxidative stress leading to oxidative damage and resulting in genomic instability, which in turn may contribute to an increased risk for cancer.

Nuclear anomalies, chromosomal aberrations and proliferation rates in cultured lymphocytes of head and neck cancer patients.

Head and neck cancers (HNC) are extremely complex disease types and it is likely that chromosomal instability is involved in the genetic mechanisms of its genesis. However, there is little information regarding the background levels of chromosome instability in these patients. In this pilot study, we examined spontaneous chromosome instability in short-term lymphocyte cultures (72 hours) from 72 study subjects - 36 newly diagnosed HNC squamous cell carcinoma patients and 36 healthy ethnic controls. We estimated chromosome instability (CIN) using chromosomal aberration (CA) analysis and nuclear level anomalies using the Cytokinesis Block Micronucleus Cytome Assay (CBMN Cyt Assay). The proliferation rates in cultures of peripheral blood lymphocytes (PBL) were assessed by calculating the Cytokinesis Block Proliferation Index (CBPI). Our results showed a significantly higher mean level of spontaneous chromosome type aberrations (CSAs), chromatid type aberration (CTAs) dicentric chromosomes (DIC) and chromosome aneuploidy (CANEUP) in patients (CSAs, 0.0294±0.0038; CTAs, 0.0925±0.0060; DICs, 0.0213±0.0028; and CANEUPs, 0.0308±0.0035) compared to controls (CSAs, 0.0005±0.0003; CTAs, 0.0058±0.0015; DICs, 0.0005±0.0003; and CANEUPs, 0.0052±0.0013) where p<0.001. Similarly, spontaneous nuclear anomalies showed significantly higher mean level of micronuclei (MNi), nucleoplasmic bridges (NPBs) and nuclear buds (NBUDs) among cases (MNi, 0.01867±0.00108; NPBs, 0.01561±0.00234; NBUDs, 0.00658±0.00068) compared with controls (MNi, 0.00027±0.00009; NPBs, 0.00002±0.00002; NBUDs, 0.00011±0.00007).The evaluation of CBPI supported genomic instability in the peripheral blood lymphocytes showing a significantly lower proliferation rate in HNC patients (1.525±0.005552) compared to healthy subjects (1.686±0.009520 ) (p<0.0001). In conclusion, our preliminary results showed that visible spontaneous genomic instability and low rate proliferation in the cultured peripheral lymphocytes of solid tumors could be biomarkers to predict malignancy in early stages.

Assessment of DNA damage using cytokinesis-block micronucleus cytome assay in lymphocytes of dilated cardiomyopathy patients.

Studies on the extent of DNA damage are undertaken to elucidate the nature and causes of genomic instability in any syndrome or disease progression in human. In this study, cytokinesis-block micronucleus cytome (CBMN Cyt) assay was employed to evaluate the extent of chromosomal instability or DNA damage in lymphocytes of patients suffering from dilated cardiomyopathy (DCM), a serious cardiac muscle disorder. Effect of DNA damage on the disease was also assessed by analysis of mutations in cardiac Troponin C type I (TNNC1) gene. Blood samples were collected from 48 DCM patients and 48 age- and sex-matched controls from Vellore region of South India. Significantly high frequencies of micronuclei (MNi) and genomic damage such as nuclear buds (NBUDs) and nucleoplasmic bridges (NPBs) were observed in the patient group as compared with the control group (P < 0·001). Molecular analysis revealed that no mutations were found in the TNNC1 gene. It was observed that although there was a high frequency of DNA damage in the lymphocytes of the patients, no correlation between severity of the phenotype and the frequencies of MNi, NPBs and NBUDS could be established. Our study appears to be the first one in which chromosomal instability was estimated using CBMN Cyt assay for DCM patients. Studies with a larger population size may help in validating the use of genetic markers for establishing frequencies and type of DNA damage in DCM. It will also help in understanding the effect of DNA damage on this disease.

Genotoxic assessment in peripheral blood lymphocytes of post-polio individuals using sister chromatid exchange analysis and micronucleus assay.

Environmental pollution is a complex issue because of the diversity of anthropogenic agents, both chemical and physical, that have been detected and catalogued. The consequences to biota from exposure to genotoxic agents present an additional problem because of the potential for these agents to produce adverse change at the cellular and organism levels. Past studies in virus have focused on structural damage to the DNA of environmental species that may occur after exposure to genotoxic agents and the use of this information to document exposure and to monitor remediation. In an effort to predict effects at the population, community and ecosystem levels, in the present study, we attempt to characterize damage occurring through genotoxic agents like 5-bromo-2-deoxyuridine, BrdU, using sister chromatid exchange technique and the formation of micronuclei (MN) in the peripheral lymphocytes of the post-polio syndrome sequelae affected by poliovirus. Analysis of structural chromosomal aberrations (CAs) and involvement of the specific chromosome break were pursued in this study. They revealed a significantly higher incidence of CAs (chromatid and chromosome breaks) in patients compared with controls, where the specific chromosome break has emerged as specific. Also, the maximum numbers of breaks were found to be in chromosome 1 at the position 1p36.1. The results also suggest a correlation between CAs and content of MN.

Frequencies of X-ray induced chromosome aberrations in lymphocytes of xeroderma pigmentosum and Fanconi anemia patients estimated by Giemsa and fluorescence in situ hybridization staining techniques

Linfócitos sanguíneos de pacientes com xeroderma pigmentosum (XP) e anemia de Fanconi (FA) foram avaliados quanto à sensibilidade, à ionizaçäo radiante estimando-se a freqüência de aberraçöes cromossômicas (CA) induzidas por raios-X (1 e 2 Gy). As freqüências de aberraçöes no genoma inteiro foram estimadas em preparaçöes de linfócitos irradiados nas fases G0 e G2 coradas com Giemsa. As freqüências de translocaçöes e dicêntricos envolvendo os cromossomos 1 e 3 e o cromossomo X foram determinadas em lâminas coradas por hibridizaçäo fluorescente in situ (FISH). Um aumento em todos os tipos de CA foi observado em linfócitos XP e FA irradiados na fase G0 quando comparados a controles. A freqüência de dicêntricos e anéis foi 6-27 por cento maior (com 1 e 2 Gy) em linfócitos XP e 37 por cento maior (com 2 Gy) em linfócitos FA do que em controles, enquanto que as deleçöes cromossômicas foram mais freqüentes em linfócitos XP irradiados (30 por cento com 1 Gy e 72 por cento com 2 Gy) do que em controles e 28-102 por cento mais freqüentes em linfócitos FA. Em linfócitos irradiados na fase G2 a freqüência total de CA foi 24-55 por cento mais elevada em linfócitos XP do que em controles. Na maior parte dos casos as freqüências de translocaçöes foram maiores do que as freqüências de dicêntricos (21/19).