Nuclear abnormalities in cells from nasal epithelium: a promising assay to evaluate DNA damage related to air pollution in infants

ObjectivesThis study intends to provide a quick, easy, and inexpensive way to assess nuclear abnormalities such as micronuclei and bud frequencies; binucleated, karyorrhectic, karyolytic, pycnotic, and condensed chromatin cells in nasal scrapings of infants, which are particularly important for conducting genotoxic studies related to the inhaled atmosphere in pediatric populations.MethodsNasal swab samples were collected from 40 infants under 12 months of age using a small cytobrush. 2,000 cells from each infant sample were analyzed and classified according to the frequency of nuclear abnormalities.ResultsRates of nuclear abnormalities found agree with values reported in other studies of neonates and children. This study found 0.13% of cells with micronuclei; 1.20% karyorrhexis; 0.03% pyknosis; 10.85% karyolysis; 1.11% condensed chromatin; 0.54 binucleated cells; and 0.02% nuclear bud. Differences were not observed between genders or environmental passive smoking, nor was any age correlation found.ConclusionThe assay proposed here is suitable for assessing the frequency of nuclear abnormalities from nasal cells in infants.     

XRCC1 gene variants and possible links with chromosome aberrations and micronucleus in active and passive smokers

Tobacco addiction is a major risk for diseases such as cancers, heart attack, etc. Tobacco smoke constitutes environmental toxins that are the major preventable leading cause of death worldwide. We investigated the influence of tobacco smoke on cytogenetic parameters (chromosomal aberrations and micronuclei) and the influence of XRCC1 arg399gln polymorphism on the cytogenetic parameters of the exposed subjects. The cases for this study include active and passive smokers. They were divided into three groups in accordance with duration of exposure to tobacco smoke. We observed changes in the frequency of chromosomal aberrations and micronuclei among the exposed subjects and controls. Of the three groups of exposed subjects, group III of active smokers and group III of passive smokers showed higher number of chromosomal aberrations and micronuclei when compared to controls, group I and group II of active and passive smokers. The XRCC1 arg399gln polymorphic variant gln/gln, influenced the extent of genotoxic damage in chromosomes and frequency of in micronuclei the three variants (arg/arg, arg/gln and gln/gln), gln/gln harbored significantly (P < 0.05) higher number of aberrations than the arg/arg and arg/gln. In this context, the results observed in our study indicated that the single nucleotide polymorphism on XRCC1codon 399 influenced the frequencies of chromosomal aberrations and micronuclei.     

A cytogenetic approach to the effects of low levels of ionizing radiations on occupationally exposed individuals

The aim of the present study was to assess occupationally induced chromosomal damage in hospital workers exposed to low levels of ionizing radiation. Thirty-two interventional cardiologists, 36 nuclear medicine physicians and 33 conventional radiologists were included in this study, along with 35 healthy age- and sex-matched individuals as the control group. We used conventional metaphase chromosome aberration (CA) analysis, cytokinesis-block micronucleus (MN) assay as important biological indicators of ionizing radiation exposure. Occupational dosimetry records were collected over the last year (ranged from 0.25 to 48 mSv) and their whole life exposure (ranged from 1.5 to 147 mSv). The results showed significantly higher frequencies of dicentric and acentric CAs (p < 0.001) and MN (p < 0.01) in all exposed groups than in the controls. Taking all the confounding factors into account, no obvious trend of increased chromosomal damages as a function of either duration of employment, exposed dose, sex or age was observed. Interventional cardiologists had the highest rates of CA and MN frequencies between the worker groups, though the differences were not significant. These results indicate that long term exposure to low dose ionizing radiation could result in DNA damage. Hence, the personnel who work in the hospitals should carefully apply the radiation protection procedures.     

Increased frequency of micronuclei in diabetes mellitus patients using pioglitazone and glimepiride in combination

Micronuclei frequency is a sensitive biomarker used to evaluate the genotoxicity induced by xenobiotics. Pioglitazone and glimepiride were associated with genotoxicity in experimental studies conducted in rats. Considering the lack of published reports on genotoxicity in T2DM patients using pioglitazone and glimepiride drugs in combination, current study aimed to assess whether the case and control groups significantly differ from each other in the frequency of micronuclei. Subjects comprise 127 T2DM patients (35–65 years old) under pioglitazone and glimepiride treatment for >5 years and control group of 140 age matched healthy controls (38–69 years old). Exfoliated oral mucosa cells were collected from buccal mucosa of all subjects and Feulgen/Fast-Green method was followed to screen for micronuclei. Factors such as gender, food habits, living areas and occupation have not shown significant association with the variation in micronuclei frequency among the studied subjects. However, T2DM patients under long term treatment of pioglitazone and glimepiride in combination, showed increased frequency of micronuclei as compared to controls (p < 0.001). Current study suggests that the micronuclei assay can be used as a constituent among the panel of biomarkers to assess genotoxicity in T2DM patients under long term antihyperglycemic drug therapy.     

Prospective follow-up studies found no chromosomal mutagenicity of methylphenidate therapy in ADHD affected children

Five to ten percent of all children suffer from attention-deficit/hyperactivity disorder (ADHD), which is often treated with the central nervous stimulant methylphenidate (MPH). In 2005 controversy arose due to a report of enhanced cytogenetic effects in 12 children after 3 months of MPH treatment. Since then, several prospective studies have been performed and published, which are summarized here. A table comparing the micronucleus frequencies, a marker investigated in all of these studies, is presented. An induction of cytogenetic effects by MPH was only reported in one, the 2005 study by El-Zein et al., while all other studies, with now altogether 110 MPH-exposed individuals, showed no elevation. To address the question of long-term use of MPH, we published the data of 30 chronically treated children and also saw no difference compared to untreated children. Here, we report as new follow-up data that an additional 12 months time point in a small group of 12 children who had begun MPH therapy within our published study also did not reveal elevated cytogenetic damage. Furthermore, a previously unpublished analysis of urinary 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG; a non-invasive biomarker for DNA-base oxidation and its repair) in 11 children before and after 3 months of MPH exposure yielded no significant difference. Since gene mutations may not necessarily manifest as chromosomal aberrations, micronuclei or SCEs, we discuss the available data from animal models, which also do not reveal a mutagenic potential of MPH. Although the only two available epidemiological studies do not report elevated risk for MPH exposure, the results are not conclusive yet, and further monitoring of exposed populations is suggested.     

新癀片对荷S_(180)小鼠的肿瘤生长及免疫功能的影响

目的 :探讨新癀片对荷S180 小鼠的肿瘤生长及免疫功能的影响。方法 :采用小鼠S180 实体瘤模型 ,以新癀片灌胃治疗 ,观察新癀片对荷S180 小鼠的瘤体比、抑瘤率、胸腺和脾脏的脏器系数及骨髓PCE微核率的变化。结果 :新癀片具有减少瘤体比、明显抑制肿瘤生长、增加脾重和外周血白细胞数目的作用 ,但对骨髓PCE微核率无明显影响。结论 :新癀片具有抑制S180 肿瘤生长和增强其细胞免疫的功能。     

鲜皇浆的抗辐射损伤作用研究

目的:探讨鲜皇浆对小鼠辐射损伤的保护作用。方法:将160只小鼠随机分为3个试验组,剂量分别为0.80、1.78、5.00g/kg,另设一个辐射对照组,每天灌胃1次,连续30d后,各组均以60Co射线进行一次全身照射,并继续给样品,根据检测指标选择不同的照射剂量。辐照前、辐照后第3和14天进行外周血细胞计数;辐照后第3天进行骨髓有核细胞计数和骨髓细胞微核试验;辐照后第7天进行超氧化物歧化酶(SOD)活力测定;辐照后第14天测定血清溶血素。结果:3个试验组小鼠外周血白细胞数、骨髓有核细胞数和血清溶血素含量明显高于辐射对照组(P<0.05),骨髓微核率明显低于辐射对照组(P<0.05),血清SOD活力高于辐射对照组,但无显著性差异(P>0.05)。结论:鲜皇浆对辐射损伤具有一定的防护作用。     

培养人淋巴细胞微核测试法检测非整倍体诱变剂的研究

直接用培养人淋巴细胞微核测试系统，采取控制化学品处理培养细胞和恢复时间，对已知非整倍体诱变剂长春新碱进行微核检测，实验结果显示，在设定的微核检测程序中，阴性对照和断裂剂丝裂霉素Ｃ未诱发微核率的显著增加（Ｐ〉０．０５）而ＶＢＬ却引起ＭＮＦ显著增加（Ｐ〈０．０１）。结果揭示培养人外周血淋巴细胞微核测试法可能成为一种新的人类化学品非整倍体诱变剂的检测方法。     

刺玫果对烹饪油烟引起小鼠骨髓PCE微核率增高的影响

本文研究了刺玫果对烹饪油烟引起的小鼠骨髓嗜多染红细胞微核率的影响。结果表明,烹饪油烟各实验组的小鼠骨髓嗜多染红细胞微核率明显高于阴性对照组(P<0.01),且呈现剂量-反应关系,刺玫果明显降低烹饪油烟诱发的微核率。     

硝酸羟胺诱导大鼠骨髓细胞微核的初步研究

目的探讨不同剂量硝酸羟胺对大鼠骨髓细胞核的影响.方法腹腔注射不同浓度的硝酸羟胺溶液,连续5 d染毒,分别于染毒后6 h、24 h、3 d、7 d、14 d、28 d取大鼠胸骨骨髓,计数大鼠骨髓细胞微核率并评价硝酸羟胺对大鼠的毒性作用程度.结果大鼠腹腔注射100 mg/kg剂量组在6 h、24 h和28 d时间点,75 mg/kg剂量组在28 d时间点与对照组相比有显著差异.结论腹腔注射硝酸羟胺可诱导大鼠染色体损伤.