Chromosome damage in peripheral lymphocytes of sheep induced by chlorine in drinking water

The potential of chromosomal damage associated with the effects of chlorine in drinking water was evaluated using chromosome aberrations and micronuclei as cytogenetic endpoints in the lymphocytes of peripheral blood of ewe lambs. The study assessed the in vivo effects of high chlorine doses (1.8 mg l(-1), based on Savo-Super disinfectant) in drinking water on the peripheral lymphocytes of sheep after 30 days. The frequency of aberrant cells (AB.C.) in the experimental and control groups was 31.80+/-13.68% AB.C. and 4.50+/-2.07% AB.C. respectively, and the increased AB.C. in the treated group was highly significant (P=/<0.001). In the experimental group chromatid breaks (26.20+/-10.47%) and gaps (24.20+/-13.94%) were the dominant types of aberrations, but statistically significant chromosome gaps and exchanges were also present. The frequency of micronuclei in peripheral lymphocytes of sheep in the control group was 21.17+/-4.36 per 1,000 binucleated cells and 64.20+/-22.51 per 1,000 binucleated cells in the experimental group. A significant increase in the frequency of micronuclei in peripheral lymphocytes of sheep was observed between the two groups (P=0.001).     

Relevance of apple consumption for protection against oxidative damage induced by hydrogen peroxide in human lymphocytes

In a single-dosing crossover study, we investigated the ability of apple fruit consumption to protect human lymphocytes against peroxide-induced damage to DNA. Six healthy, non-smoking male volunteers were placed for 2d on an antioxidant-poor (AP) diet. After 48h of AP diet, the volunteers were required to consume a homogenate obtained from 600g of red delicious unpeeled apples or water (500 ml); blood samples were collected 0, 3, 6 and 24 h post-consumption. To evaluate whether the apple intake was sufficient to restore resistance of DNA to oxidative damage, for each subject at any time point the plasma total antioxidant activity, reactive oxygen species (ROS) formation and induction of micronuclei (MN) in isolated lymphocytes following hydrogen peroxide (H2O2) treatment were measured. Results indicated a significant inhibition (58%, P <0.05) of H2O2-induced MN frequency in the plasma samples collected at 3 h after apple consumption, as compared with plasma samples collected at 0 h (4.17 (SD 1.83) v. 9.85 (SD 1.87) MN/1000 binucleated (BN) cells, respectively). A gradual return towards the value observed at 0 h was recorded starting from 6 to 24 h. MN frequency induced by H2O2 was significantly influenced by plasma total antioxidant activity (r = -0.95, P <0.05) and by the increase of intracellular ROS formation (r = 0.88, P <0.05). These findings suggest that the consumption of whole apple provides a useful dietary source of active scavengers to protect cells and tissue from oxidative stress and related DNA injury.     

Chromosome damage in passive smoker females

Current epidemiological data associates passive smoking with health hazards which not only affects the passive smoker but also affects the offsprings of passive smoker females. To determine the effect of cigarette smoke on the chromosomes of passive smoker females who were still in the childbearing age, the micronucleus (MN) frequency in 20 passive smoker females (spouse smoker) who had been exposed to cigarette smoke for at least 5 years was compared to the MN frequency in 20 control subjects (females with non-smoking spouse) all in the age group 31-39 years. The MN frequency among passive smoker female group ranged from 16-27 MN/500 cytokinesis blocked (CB) binucleated cell, with a mean of 21.1 +/- 3.7, while the MN frequency among the control group ranged from 3-11 MN/500 CB binucleated cell, with a mean of 8 +/- 1.7. The difference is statistically significant (t = 14.2, p < 0.01). Applying the correlation coefficient test between age and MN frequency, a weak positive though non significant correlation was found between age and MN frequency in the passive smoker female group (R = 0.11, p = 0.630) while an intermediate positive but still non significant correlation was found between age and MN frequency in the control (R = 0.26, p = 0.27). There was a positive correlation between the duration of exposure to cigarette smoke and the MN frequency, but this was statistically non significant (R = 0.33, p = 0.125). The results emphasize that mothers especially in the childbearing age should not be exposed to cigarette smoke to avoid its deleterious effects on their health thus preventing any harmful effect the smoke can have on their offsprings.     

A cytogenetic study of Korean native goat bred in the nuclear power plant using the micronucleus assay

Cytogenetic and hematological analysis was performed on the peripheral blood lymphocytes (PBLs) obtained from Korean native goats bred in two nuclear power plants (Wolsong and Uljin) and a control area. The frequencies of gamma-ray-induced micronuclei (MN) in the cytokinesis-blocked (CB) lymphocytes at several doses were measured in three Korean native goats. The measurements performed after irradiation showed dose-related increases in the MN frequency in each of the donors. The results were analyzed using a linear-quadratic model with a line of best fit of y=0.1019D+0.0045D2+0.0093 (y=number of MN/CB cells and D=irradiation dose in Gy). The MN rates in the goats from the Wolsong and Uljin nuclear power plant, and the control area were 9.60+/-2.88, 6.83+/-1.47 and 9.88+/-4.32 per 1,000 CB lymphocytes, respectively. The apparent difference is not statistically significant. The MN frequencies of PBLs from goats bred in three areas means that the values are within the background variation in this experiment. The MN frequencies and hematological values were similar regardless of whether the goats were bred in the nuclear power plant or the control area.     

焦炉工人外周血淋巴细胞热休克蛋白72水平及与DNA损伤的关系

目的研究焦炉逸散物对焦炉工人外周血淋巴细胞热休克蛋白72（Hsp72）水平的影响及与DNA损伤的关系，探讨Hsp72在细胞损伤保护中的意义。方法选取267名焦炉工人和30名对照，以Western blot法检测外周血淋巴细胞Hsp72的水平，彗星试验检测DNA损伤水平，个体采样采集作业环境空气样本，高效液相色谱法测定环境苯并[a]芘浓度。结果高暴露组工人外周血淋巴细胞Hsp72水平（G±SG）和Olive尾矩（G±SG）分别为1．24±0．42和4．49±1．24，明显高于低暴露组（1．01±0．35和2．99±1．10）和对照组（0．85±0．34和2．40±1．00），差异有统计学意义（P〈0．05）。以全体研究对象Hsp72中位数为界值，将研究对象分为Hsp72高表达组和低表达组，Hsp72高表达的人数相对比率在对照组、低暴露组、高暴露组分别为36．7％、43．1％和58．3％，呈逐渐增高趋势，差异有统计学意义（P=0．003）。在Hsp72高表达组，Hsp72表达水平随着暴露等级升高而升高，其中高暴露组与对照组的差异有统计学意义（P〈0．05），但各组之间Olive尾矩的差异无统计学意义（P〉0．05）。在Hsp72低表达组中，各组Hsp72水平的差异无统计学意义（P〉0．05），而Olive尾矩随暴露等级升高而升高，其中高暴露组与低暴露组和对照组比较，差异有统计学意义（P〈0．01），且明显高于Hsp72高表达组的高暴露组工人。高暴露组Hsp72水平与Olive尾矩呈负相关（r=0．503，P〈0．01）。结论焦炉逸散物可诱导焦炉工人外周血淋巴细胞Hsp72水平升高，Hsp72对细胞DNA损伤具有保护作用。     

Genetic damage in operating room personnel exposed to isoflurane and nitrous oxide

OBJECTIVES: To evaluate genetic damage as the frequency of sister chromatid exchanges and micronuclei in lymphocytes of peripheral blood of operating room personnel exposed to waste anaesthetic gases. METHODS: Occupational exposure was measured with a direct reading instrument. Venous blood samples were drawn from 10 non-smokers working in the operating room and 10 non-smoking controls (matched by age, sex, and smoking habits). Lymphocytes were cultured separately over 72 hours for each assay with standard protocols. At the end of the culture time, the cells were harvested, stained, and coded for blind scoring. The exchanges of DNA material were evaluated by counting the number of sister chromatid exchanges in 30 metaphases per probe or by counting the frequency of micronuclei in 2000 binucleated cells. Also, the mitotic and proliferative indices were measured. RESULTS: The operating room personnel at the hospital were exposed to an 8 hour time weighted average of 12.8 ppm nitrous oxide and 5.3 ppm isoflurane. The mean (SD) frequency of sister chromatid exchanges was significantly higher (10.2 (1.9) v 7.4 (2.4)) in exposed workers than controls (p = 0.036) the proportion of micronuclei (micronuclei/500 binucleated cells) was also higher (8.7 (2.9) v 6.8 (2.5)), but was not significant (p = 0.10). CONCLUSION: Exposure even to trace concentrations of waste anaesthetic gases may cause dose-dependent genetic damage. Concerning the micronuclei test, no clastogenic potential could be detected after average chronic exposure to waste anaesthetic gas. However, an increased frequency of sister chromatid exchanges in human lymphocytes could be detected. Although the measured differences were low, they were comparable with smoking 11-20 cigarettes a day. Due to these findings, the increased proportion of micronuclei and rates of sister chromatid exchanges may be relevant long term and need further investigation.

 

     

口腔脱落细胞微核技术在丙烯腈接触人群中的应用

目的探讨口腔脱落细胞微核技术在接触丙烯腈人群遗传损伤监护中的应用价值。方法选择生产过程中接触不同浓度丙烯腈的2个工厂工人为接触组,按空气中丙烯腈浓度高低分为低浓度组(41名男性工人)和中浓度组(47名男性工人),另选择不接触任何毒物的男性工人31名为对照组,分别进行口腔黏膜脱落细胞微核和外周血淋巴细胞微核测试。结果2个丙烯腈接触组的口腔黏膜脱落细胞微核率(低浓度组:3.68‰±2.72‰;中浓度组:4.00‰±2.38‰)明显高于对照组(2.03‰±2.20‰),中浓度接触组的血淋巴细胞微核率(4.23‰±3.34‰)明显高于对照组(2.48‰±1.46‰),差异均有统计学意义(P<0.05)。在丙烯腈接触人群中,口腔黏膜脱落细胞微核试验和外周血淋巴细胞微核试验有相关关系(r=0.299~0.359,P<0.05)。结论在丙烯腈接触人群遗传损伤监护时,可用口腔黏膜脱落细胞微核试验代替外周血淋巴细胞微核试验作为筛查指标之一。     

猕猴桃汁抗环磷酰胺致突变作用的机理

目的用大鼠外周血双核淋巴细胞微核测试法（ＣＢＭＮＴ），在哺乳动物整体水平，研究猕猴桃汁抗环磷酰胺（ＣＰ）的致突变作用以及生物转化Ⅱ相酶的作用。方法测定大鼠外周血双核淋巴细胞微核细胞率及肝组织中总谷胱甘肽硫转移酶（ＧＳＴ）、尿苷二磷酸葡萄糖醛酸转移酶（ＵＤＰＧＴ）、谷氨酰胺转肽酶（γＧＴ）活性。结果猕猴桃汁对ＣＰ诱发的大鼠外周血双核淋巴细胞微核细胞率有显著抑制作用，能明显诱导大鼠肝脏总ＧＳＴ、ＵＤＧＴＰ活性，但对γＧＴ活性无显著影响。大鼠外周血双核淋巴细胞微核细胞率与总ＧＳＴ、ＵＤＧＴＰ活性呈明显负相关。结论猕猴桃汁抗ＣＰ致微核形成作用的机理可能是通过诱导机体外来化合物代谢解毒酶系，加速ＣＰ的代谢灭活     

甲醛接触人群细胞遗传学效应及个体差异

对不同甲醛接触人群外周血淋巴细胞姊妹染色单体交换（ＳＣＥ）及微核形成率的观察结果表明对照组、学生组、服务员及工人组接触甲醛浓度（ＴＷＡ）分别为０．０１１ｍｇ／ｍ３、０．５０８ｍｇ／ｍ３、０．０１７ｍｇ／ｍ３、和０．７４７ｍｇ／ｍ３，与对照组相比，工人组的ＳＣＥｓ和ＭＮ都有显著性增高，而其他两组的差异则无显著性；工人组的ＳＣＥｓ与ＭＮ之间未见有相关性，解剖实验课学生接触甲醛前后，组内的ＳＣＥｓ和ＭＮ波动范围更在，ＳＣＥｓ和ＭＮ的变化表现出明显的个体差异。提示接触较为高浓度的甲醛可诱发人群淋巴细胞实变。并受到接触剂量与遗传体质的影响。     

The effects of thymol on sister chromatid exchange,chromosome aberration and micronucleus in human lymphocytes

The genotoxic effects of thymol were investigated in human peripheral lymphocytes treated with 25, 50, 75, and 100 μg/ml concentrations of thymol for 24 and 48 h treatment periods by using sister chromatid exchange (SCE), chromosome aberration (CA), and micronucleus (MN) tests. Nuclear division index (NDI), replication index (RI), and mitotic index (MI) were also calculated in order to determine the cytotoxicity of thymol. Thymol significantly increased the SCE, especially at the lower concentrations. Thymol also increased the SCE at the highest concentrations without statistical significance. Thymol induced both the structural CA and frequency of MN at all concentrations. Thymol dose-dependently decreased the NDI for two treatment periods. Thymol decreased the RI for the 24 h treatment time without any statistical significance. However, thymol decreased the RI for the 48 h treatment time in a dose-dependent manner. Thymol also decreased the MI at the higher concentration without dose-dependent effect.     

胞质分裂阻断法及染色体畸变实验检测水质诱变性及两种方法的比较

运用人胚肺细胞胞质分裂阻断法（ＣＹ－ＭＮＴ）及染色体畸变实验（ＳＣＡ）检测了某市水源水及自来水的遗传毒性，并比较了两短测实验方法和相应的反映细胞毒性的指标ＮＤＩ（ｎｕｃｌｅａｒｄｉｖｉｓｉｏｎｉｎｄｅｘ）和ＭＩ（ｍｉｔｏｔｉｃｉｎｄｅｘ）之间的关系。结果表明：该市的水源水及自来水中的有机提取物可不同程度地诱导微核率及染色体畸变率的升高，并且各实验剂量组与ＮＤＩ、ＭＩ有很好的负相关关系，源水的相关系数分别为－０．９０４、－０．９８０，自来水的相关系数分别为－０．８８２、－０．９１８，微核率（ＭＮＢＮ，Ｍｉｃｒｏｎｕｃｌｅａｔｅｄｂｉｎｕｃｌｅａｔｅｄ）与染色体畸变率（ＳＣＡ，Ｓｔｒｕ－ｔｕｒａｌｃｈｒｏｍｏｓｏｍａｌａｂｅｒａｔｉｏｎ）及ＮＤＩ与ＭＩ有很好的相关性，源水的相关系数分别为０．８８６、０．９５８，自来水的相关系数分别为０．９９４、０．９６０。     

牛磺酸对苯并(a)芘致L-02细胞损伤保护作用

目的 研究牛磺酸对苯并(a)芘(B(a)P)致人胚肝细胞(L-02细胞)染色体损伤的保护作用.方法 以L-02细胞为靶细胞,按完全随机设计分成5组:(1)空白对照组;(2)溶剂对照组;(3)B(a)P染毒组:设12.5,25,50μmol/L3个剂量染毒细胞;(4)牛磺酸组:设1.0,2.0,4.0mmol/L3个浓度,加入培养体系后继续培养24h;(5)牛磺酸预防组:L-02细胞先以3个不同浓度的牛磺酸预处理24h,再加入25μmol/L的B(a)P培养24h.各组均设3个平行样.收获细胞后用微核实验检测染色体损伤,计算微核率和核分裂指数.结果 牛磺酸单独作用于L-02细胞时,与空白对照组比较,中、高浓度牛磺酸诱导的微核率降低,核分裂指数增高,差异有统计学意义.从低到高3个剂量B(a)P单独染毒L-02细胞诱导的微核率为(34.67±2.52),(45.33±4.16),(60.00±7.21)%.核分裂指数分别为1.326±0.034,1.228±0.006,1.148±0.012,与溶剂对照组比较微核率升高,核分裂指数降低,差异有统计学意义,且两者均呈明显的剂量-反应关系.低、中、高浓度牛磺酸预防组诱导的微核率对应为(30.33±3.51),(25.67±1.53)和(23.00±1.00)%.均比单纯25μmol/LB(a)P染毒组诱导的微核率降低,差异有统计学意义.低、中、高浓度牛磺酸预防组对应的核分裂指数为1.455±0.011,1.474±0.015和1.1492±0.013,比单纯25μmol/LB(a)P染毒诱导的核分裂指数高,差异有统计学意义,且两者均呈剂量-反应关系.结论 B(a)P能诱导肝细胞染色体损伤,且存在明显的剂量-反应关系;牛磺酸预处理对B(a)P引起的肝细胞毒性具有明显保护作用.     

Differential induction of micronuclei in peripheral lymphocytes and exfoliated urothelial cells of workers exposed to 4,4'-methylenebis-(2-chloroaniline) (MOCA) and bitumen fumes

Cytogenetic end-points used to estimate risk of genotoxic events in workers include the measurement of micronuclei (MN) in exfoliated cells, lymphocytes, and other tissues. Micronuclei are chromatin-containing bodies outside the cell nucleus resulting from contaminant-induced DNA damage. A review of 71 reports of human genotoxic responses to chemical or physical agents published between 1999 and 2001 revealed that 14% of such studies measured genotoxicity endpoints in specific target tissues relevant to the site of disease for the agent examined; 18% used endpoints in surrogate or non-target tissues but considered the relations between endpoints in surrogate and disease target tissues, and 68% measured genotoxicity endpoints in accessible tissues without reference to specific targets for disease. Methylenebis-(2-chloroaniline) (MOCA), used in polyurethane manufacture, is a suspected bladder carcinogen. Bitumen, used in road surfacing, contains skin and lung carcinogens. In this study, we aimed to compare genotoxicity in urothelial cells and in lymphocytes of workers exposed to these materials. Twelve men employed in polyurethane manufacture, twelve bitumen road layers, and eighteen hospital stores personnel (controls) were recruited and all provided blood and urine samples on the same day. Blood cultures were prepared using a cytochalasin B-block method. Exfoliated urothelial cells were collected from urine and stained for light microscopy. The number of MN in urothelial cells was higher in MOCA-exposed (14.27 +/- 0.56 MN/1000, 9.69 +/- 0.32 MN cells/1000) than in bitumen exposed workers (11.99 +/- 0.65 MN/1000, 8.66 +/- 0.46 MN cells/1000) or in control subjects (6.88 +/- 0.18 MN/1000, 5.17 +/- 0.11 MN cells/1000). Conversely, in lymphocytes, MN were higher in bitumen-exposed (16.24 +/- 0.63 MN/1000, 10.65 +/- 0.24 MN cells/1000) than in MOCA-exposed workers (13.25 +/- 0.48 MN/1000, 8.54 +/- 0.14 MN cells/1000) or in control subjects (9.24 +/- 0.29 MN/ 1000, 5.93 +/- 0.13 MN cells/1000). The results of this study suggest that genotoxins can cause different rates of micronuclei formation in different tissues. Thus, the sensitivity and relevance to cancer risk may be greater if the tissues selected for genotoxicity studies reflect the target tissue for the chemicals concerned.     

Nutritional assessment of vitamin E in malnourished patients with AIDS

Malnourished patients with acquired immunodeficiency syndrome (AIDS) may have low serum levels and reduced intake of alpha-tocopherol, mainly in the presence of acute-phase response. The aims of this study were to compare intake and serum levels of alpha-tocopherol between malnourished (MN) and non-malnourished (NMN) AIDS patients and to correlate alpha-tocopherol intake and serum levels. Undernutrition was defined as having a body mass index lower than 18. 5 kg/m(2) or a height-creatinine index lower than 70%. A semiquantitative food frequency questionnaire assessed alpha-tocopherol intake. High-performance liquid chromatography determined vitamin serum levels. The patients were divided into MN (n = 14) and NMN (n = 15) groups. There were no statistical differences in relation to clinical findings between MN and NMN, respectively, including moniliasis (7/14 versus 4/15), neurocryptoccocosis and neurotoxoplasmosis (6/14 versus 6/15), pulmonary tuberculosis (4/14 versus 2/15), and fever (1/14 versus 3/15). MN and NMN groups had similar peripheral blood CD(4) levels (111.4+/-87.1 versus 124.4+/-90.9 cells/mm(3)), and both groups had similar and adequate alpha-tocopherol intake (MN = 50.0+/-11.0 versus NMN = 47.2+/-16.5 mg) and serum levels (MN = 17.8+/-7.2 versus NMN = 19.8+/-6.3 micromol/L). Vitamin E intake and serum levels did not show a significant correlation (r = -0.22, P 0.05). Protein-energy nutrition status and acute-phase response were not factors determining vitamin status among AIDS patients.     

Maternal and gestational factors and micronucleus frequencies in umbilical blood: the NewGeneris Rhea cohort in Crete

Background: The use of cancer-related biomarkers in newborns has been very limited.Objective: We investigated the formation of micronuclei (MN) in full-term and preterm newborns and their mothers from the Rhea cohort (Crete), applying for the first time in cord blood a validated semiautomated analysis system, in both mono- and binucleated T lymphocytes.Methods: We assessed MN frequencies in peripheral blood samples from the mothers and in umbilical cord blood samples. We calculated MN in mononucleated (MNMONO) and binucleated (MNBN) T lymphocytes and the cytokinesis block proliferation index (CBPI) in 251 newborns (224 full term) and 223 mothers, including 182 mother–child pairs. Demographic and lifestyle characteristics were collected.Results: We observed significantly higher MNBN and CBPI levels in mothers than in newborns. In newborns, MNMONO and MNBN were correlated (r = 0.35, p < 0.001), and we found a moderate correlation between MNMONO in mothers and newborns (r = 0.26, p < 0.001). MNMONO frequencies in newborns were positively associated with the mother’s body mass index and inversely associated with gestational age and mother’s age, but we found no significant predictors of MNBN or CBPI in newborns.Conclusions: Although confirmation is needed by a larger study population, the results indicate the importance of taking into account both mono- and binucleated T lymphocytes for biomonitoring of newborns, because the first reflects damage expressed during in vivo cell division and accumulated in utero, and the latter includes additional damage expressed as MN during the in vitro culture step.     

X线修复交叉互补基因1多态性与1,3-丁二烯致接触工人染色体损伤易感性关系的研究

目的探讨DNA损伤修复基因X线修复交叉互补基因1(XRCC1)多态性在1,3-丁二烯致外周血淋巴细胞染色体损伤易感性中的作用。方法采用胞质分裂阻滞微核试验方法(CB-MN)评价166名1,3-丁二烯接触工人和41名正常人染色体损伤水平,应用聚合酶链反应-限制性片段多态性技术(PCR-RFLP)对接触工人第19染色体上的XRCC1第6外显子194密码子,第9外显子280密码子和第10外显子399密码子进行多态性检测。结果接触组和对照组的微核发生率分别为(3.39±2.42)‰和(1.48±1.26)‰,差异有显著性(P0.01)。高剂量接触组工人比低剂量接触组工人更容易发生染色体损伤(FR=1.30,95%CI1.14～1.53,P0.05)。XRCC1194突变基因携带个体的微核发生率比野生纯合型个体显著增高(FR=1.13,95%CI1.07～1.27,P0.05);XRCC1280突变纯合型个体的微核率较野生纯合型显著增加(FR=1.67,95%CI1.10～2.42,P0.05);XRCC1399杂合型个体以及杂合型和突变纯合型个体的微核率均显著增加(FR=1.26,95%CI1.03～1.53;FR=1.24,95%CI1.03～1.49,P0.05)。CAG/TGG双体型个体微核率显著降低,结论 XRCC1194、280、399突变位点携带工人染色体损伤风险增高。     

Effect of a low-dose ethinylestradiol and gestodene in combination on the frequency of micronuclei in human peripheral blood lymphocytes of healthy women in vivo

BACKGROUND: Since most oral hormonal contraceptives contain a fixed combination of ethinylestradiol and gestodene as an estrogenic/progestogenic component, we decided to evaluate the possible mutagenic effect of a low-dose contraceptive pills containing 20 microg ethinylestradiol and 75 microg gestodene. METHODS: A total of 30 healthy women received hormonal contraception during six consecutive menstrual cycles. A single daily dose was 20 microg ethinylestradiol and 75 microg gestodene. The pills were taken orally in a monthly cycle of 3 weeks on and 1 week off. In the investigation of the mutagenic effect of these contraceptive pills in vivo, the cytokinesis block micronucleus (CBMN) test was used, and the frequency of micronuclei (MN) in peripheral blood lymphocytes was determined. RESULTS: Average MN frequency in women before therapy was 7.40 +/- 0.75 MN/1000 analyzed cells, and after therapy was 7.37 +/- 0.59 MN/1000 analyzed cells (p > 0.05). CONCLUSION: Our data suggest that oral contraception with 20 microg ethinylestradiol and 75 microg gestodene in combination during six consecutive menstrual cycles does not induce micronuclei in peripheral blood lymphocytes of women.     

Cytogenetic radiosensitivity of g0-lymphocytes of breast and esophageal cancer patients as determined by micronucleus assay

Enhanced chromosomal radiosensitivity is a feature of many cancer predisposition conditions, indicative of the important role of chromosomal alterations in carcinogenesis. In this study the cytokinesis-blocked micronucleous assay was used to compare the radiosensitivity of blood lymphocytes obtained from Iranian breast or esophageal cancer patients (n = 50, n = 16; respectively) with that of control individuals (n = 40). For each sample, one thousand binucleate lymphocytes were analyzed before and after in vitro exposure to 3 Gy of gamma rays. The radiation-induced frequency of micronucleus was significantly higher in the breast cancer group (261/1,000 binucleated cells) than in esophageal cancer group (241/1,000 binucleated cells, P < 0.01) or in the control group (240/1,000 binucleated cells, P < 0.01). The results indicate that breast cancer patients are more radiosensitive compared to normal healthy individuals or esophageal cancer patients. Increased radiosensitivity could be due to defects in DNA repair genes involved in breast cancer formation. Since patients with esophageal cancer did not show elevated radiosensitivity, it is assumed that the contribution of radiosensitivity-related genes to the development of esophageal cancer may be smaller than the contribution of those genes to breast cancer.     

Sister chromatid exchanges and micronuclei in peripheral lymphocytes of shoe factory workers exposed to solvents

We examined sister chromatid exchanges (SCEs) and micronuclei (MN; cytokinesis-block method) in cultured peripheral lymphocytes from 52 female workers of two shoe factories and from 36 unexposed age- and sex-matched referents. The factory workers showed an elevated level of urinary hippuric acid, a biomarker of toluene exposure, and workplace air contained high concentrations of various organic solvents such as toluene, gasoline, acetone, and (in one of the plants only) ethylacetate and methylenediphenyl diisocyanate. The shoe factory workers showed a statistically significant higher frequency of micronucleated binucleate lymphocytes in comparison with the referents. This finding agreed with three preliminary MN determinations (each comprising 27-32 shoe workers and 16-20 controls) performed in one of the plants 2-5 years earlier. The shoe factory workers also had a lower average level of blood hemoglobin than the referents. In contrast, no difference was found between the groups in SCE analysis. Smokers showed significantly higher mean frequencies of SCEs per cell and high frequency cells (HFC) than nonsmokers. Aging was associated with increased MN rates and reduced cell proliferation. Polymorphism of the glutathione S-transferase M1 gene (GSTM1) did not affect the individual level of SCEs; but in smoking shoe workers an effect of the occupational exposure on the frequency of micronucleated cells could be seen only in GSTM1 null subjects. The low prevalence of the glutathione S-transferase T1 (GSTT1) null genotype precluded the evaluation of the influence of GSTT1 polymorphism. Our results show that the shoe factory workers have experienced genotoxic exposure, which is manifest as an increase in the frequency of MN, but not of SCEs, in peripheral lymphocytes. The exposures responsible for the MN induction could not be identified with certainty, but exposure to benzene in gasoline and methylenediphenyl diisocyanate may explain some of the findings.     

Assessment of genetic damage among chewers of mixture containing mainly areca nut and tobacco

Chewing mixture containing areca nut and tobacco is believed to be associated with oral cancer. Habit of chewing such mixture is prevalent among South Asian countries. This study aimed to evaluate the genotoxic effect of areca nut and tobacco on human lymphocytes. Peripheral blood from 107 subjects (nonchewers, 48; chewers, 59, including 20 subjects with oral submucous fibrosis [OSMF]) analyzed by cytokinesis-block micronucleus (CBMN) and alkaline comet assay. Nuclear anomalies, namely, binucleated cells with micronuclei (BN MN), total MN, nucleoplasmic bridge, and nuclear buds were higher in chewers whereas elevation in BN MN and total MN were significant among subjects with OSMF than nonchewers. DNA damage assessed by comet assay showed increased percentage of Tail DNA, Tail moment, and Olive tail moment among chewers as well as OSMF subjects. Significant positive correlation was observed between induction of CBMN and consumption of quids per day (r = .280, P = .033). RESULTS: suggested cytotoxic and genotoxic potential of mixture containing areca nut and tobacco.