胃癌患者外周血淋巴细胞微核，SCE和染色体畸变的研究

本文分析观察14例胃癌患者和14例正常健康人外周血淋巴细胞的微核,SCE和染色体畸变,结果发现胃癌患者微核率,SCE频率和染色体对畸变率均高于正常对照组,经统计学分析表明的两组之间差异显著,认为染色体不稳定可能是胃癌发生的物质基础。     

宫颈癌患者外周血淋巴细胞姐妹染色单体互换率及放疗前后染色体畸变率

本文对20例宫颈癌患者,20例正常人进行自发SCE频率以及宫颈癌患者放射线治疗前后染色体畸变的观察。结果表明:患者的SCE率为9.28±0.34/细胞,明显高于正常对照组(P<0.001),同时发现患者染色体数目及结构发生明显异常(P<0.01)。经放射线治疗后,染色体数目及结构异常与放疗前相比有显著改变,说明放射线虽可杀伤肿瘤细胞,但对正常细胞有较严重的损伤作用。本实验反映了癌患者淋巴细胞DNA复制后修复能力较正常人低,存在一定的遗传不稳定性。     

原发癌及骨转移瘤患者外周血淋巴细胞姐妹染色单体交换频率及微核率的研究

目的 通过对原发癌及骨转移瘤患者外周血淋巴细胞姐妹染色单体交换(sister chromatid exchanges,SCE)率和微核(micronuclei,MN)率的研究,来探讨细胞癌变中DNA的变化.方法 检测正常人、原发癌和骨转移癌的外周血淋巴细胞姐妹染色单体交换率和微核率,并比较结果.结果 有原发肿瘤的患者姐妹染色单体交换率和微核率增高,而骨转移瘤患者的姐妹染色单体交换率和微核率与无转移瘤患者比较,两者存在显著差异.结论 骨转移瘤患者的姐妹染色单体交换率和微核水平损伤严重,姐妹染色单体交换率和微核率能敏感反映DNA的损伤情况,故此姐妹染色单体交换率和微核率检测被用作快速检测环境中诱变、致癌因素的灵敏方法之一.     

BrdU诱发食管上皮重度增生患者染色体畸变与姐妹染色单体互换的观察

食管癌高发区涉县26例未经治疗的食管上皮重度增生患者与26例健康人经BrdU（5溴脱氧嘧啶苷）作用的染色体畸变率和SCE频率。患者SCE平均每中期分裂相为7.47±O.26;健康人为7.61±0.41,两者无显著差异（P>0.05）。食管上皮重度增生患者中有13例有吸烟史,比12例无吸烟史者SCE（7.95和6.96）有显著增高（P<0.01）。另外,经BrdU诱导的重增患者染色体畸变率（1.74％）与健康人（0.23％）比,两者差异极为显著（P<0.001）。而重增患者经BrdU诱导组（1.74％）也明显高于未经诱导组（0.77％）的染色体畸变率（p<0.05）。未发现畸变率的增高与吸烟、家族史有关。说明食管上皮重度增生患者畸变率增高与BrdU诱发有一定关系,提示食管上皮重增患者遗传物质与正常人有所不同,对诱变物的反应较健康人敏感。     

姐妹染色单体交换的研究进展

姐妹染色单体交换(sister chromatid exchange,SCE)是反映DNA损伤和遗传不稳定性的敏感指标,SCE技术作为一种简便和敏感的遗传学指标,它在诱变和肿瘤研究等领域中的应用十分广泛.此外,SCE技术为深入研究染色体分子结构、DNA复制、损伤和修复、染色体畸变和细胞周期等重要的基础问题提供了有用的工具.     

乙肝妊娠患者孕早期绒毛姐妹染色单体交换率的研究

目的 探讨乙肝患者体内遗传物质的损伤情况。方法 选择正常对照组20例，单纯HbsAg（＋）增高组16例，乙肝组16例，乙肝恢复组10例，HBsAg、抗HBe、抗HBc三阳组12例，脂肪肝组16例，做孕早期绒毛SCE率的检测。结果 正常组、单纯HBsAg（＋）增高组，乙肝组各组间自发和诱发SCE逐步增高，且各组间均有显著差异；乙肝恢复组SCE下降；其他肝病患者SCE均较低。结论 乙肝妊娠妇女体内出现DNA损伤及修复功能障碍。     

原发性肝癌患者及其直系亲属外周血淋巴细胞姐妹染色单体互换率的观察分析

对15例原发性肝癌、30例直系亲属和13名正常人外周血淋巴细胞作了姐妹染色单体互换频率的观察分析,结果这三组间平均数值为阶梯形分布(10.413±1.877,7.330±0.769,5.608±0.258)三组间比较均有显著差异(p<0.01)目前已证实原发性肝癌为环境因素与遗传因素协同作用的多基因病。     

牛白血病姐妹染色单体交换频率与微量元素变化、泰氏锥虫感染相关性的研究

用外周血淋巴细胞短期培养法,对64头奶牛进行姐妹染色单体交换(SCE)频率的观察,结果表明,淋巴肉瘤牛、血检和MID双阳性牛、MID单阳性牛以及健康对照牛SCE/细胞值分别为9.36±0.349(S·E),6.60±0.495,4.89±0.379和3.59±0.328,各组之间有极显著差异(P<0.01)。同时,用等离子体源发射光谱分析法对牛毛Zn、Ni、Mn、Cu、Co、Pb、Mo、Cr、Ba、B10种元素进行测定,发现MID单阳性牛、血检和MID双阳性牛、淋巴肉瘤牛被毛中Mn含量依次显著降低(P<0.05),与SCE呈显著性负相关(r=-0.969);Co含量依次增高,与SCE呈正相关(r=0.814);Cu/Zn值与SCE呈正相关(r=0.783)。用泰氏锥虫间接红细胞凝集试验(IHA)检测泰氏锥虫感染情况,发现血检和MID双阳性中、MID单阳性牛以及健康对照牛IHA阳性率分别为86.18%,4(?).45%,和31.25%,而淋巴肉瘤牛均为阳性,与SCE呈正相关(r=0.753),具有显著性意义(P<0.05)。     

铅诱发人类染色体畸变和微核的研究

对５９例根据国家标准临床确诊为铅吸收，轻度中毒，中度中毒的工人和１５例对照进行了微核率的测定，染色体畸变率的测定。结果轻度中毒组，中度中毒组的微核率，染色体畸变率，都与对照组有显著差异。     

Diethylstilbestrol-diphosphate induces chromosomal aberrations but not sister chromatid exchanges in murine bone marrow cells in vivo

Diethylstilbestrol diphosphate (DES-dp) clastogenesis was examined in the bone marrow of C57B1/6 male and female mice. Significant and sex-related dose effects were observed for the induction of chromatid-type chromosomal aberrations and for the inhibition of cellular proliferation. Females were more sensitive to the effects of DES-dp than males when assessed for either induced chromosomal aberrations or proliferative inhibition. Contrary to other published results, we did not observe either an increase in sister chromatid exchanges or an increased incidence of aneuploidy. Ovariectomy reduced the ability of DES-dp to inhibit cellular proliferation and decreased the high degree of variability between animals at high doses of DES-dp. The results of our studies show that DES is a clastogenic agent in vivo which may relate to its carcinogenicity.     

Quinoline-induced chromosome aberrations and sister chromatid exchanges in rat liver

Induction of chromosome aberrations and sister chromatid exchanges (SCEs) was studied in hepatocytes of F344 rats exposed in vivo to the hepatocarcinogen quinoline (Q). Hepatocytes were isolated 4–48 hr after a single dose of 200 mg/kg body weight or 24 hr after 28 repeated doses (once a day) of 25–200 mg/kg body weight/day by gastric intubation, and allowed to proliferate in Williams' medium E supplemented with epidermal growth factor. Cells were fixed after a culture period of 48 hr. A single dose of Q induced chromosome aberrations in up to 22% of metaphase cells, and SCEs with a frequency of up to 1.27 per chromosome 12 hr after the dose, while the control values were 1% and 0.63 per chromosome, respectively. Treatment with 28 repeated doses of Q induced significant chromosome aberrations and SCEs dose-dependently. Cytogenetic damage induced in the liver by repeated doses of Q was greater than induced by a single dose. Furthermore, Q induced replicative DNA synthesis in the liver, but failed to induce micronucleus formation in the bone marrow. The noncarcinogen 8-hydroxyquinoline was also examined and found to be essentially non-genotoxic to rat liver. These results show that Q is a genotoxic carcinogen to rat liver and the present method of in vivo cytogenetic assay should be useful for evaluating the genotoxicity of hepatocarcinogens. Environ. Mol. Mutagen. 30:459–467, 1997 © 1997 Wiley-Liss, Inc.     

Sister chromatid exchanges induced in rabbit lymphocytes by ethylene oxide after inhalation exposure

Ethylene oxide, which is the simplest epoxide and an extremely important commercial compound, has been used by many investigators as a model compound to study mutagenicity by alkylation of DNA. Knowledge of in vivo dose-effect relations under experimental conditions may provide further insight into the dynamics of the sister chromatid exchange (SCE) response. It may also provide information on temporal aspects of sampling design for human worker populations. Groups of four male New Zealand white rabbits were exposed in inhalation chambers to 0, 10, 50, and 250 parts per million (ppm) ethylene oxide for 6 hr a day, 5 days a week, for 12 weeks. Peripheral blood samples were taken before the start of exposure, at intervals during exposure, and up to 15 weeks after the end of exposure to measure SCE rates in peripheral lymphocytes as well as standard hematological endpoints. Additionally, the level of reduced glutathione (GSH) in liver and blood was measured in a set of concurrently exposed animals at the end of the 12-week exposure. Results show that exposure to 10 ppm does not cause a detectable increase in SCE rates. However, exposure to 50 and 250 ppm does cause an increase in SCEs that decreases after exposure ends, but still remains above baseline levels 15 weeks after exposure. Hematological and GSH measurements did not differ between control and exposed groups. These results indicate that inhalation exposure to the mutagenic alkylating agent ethylene oxide results in a dose-related SCE effect, and that SCE is a more sensitive indicator of exposure than either standard hematological end points or GSH levels.     

Induction by inorganic metal salts of sister chromatid exchanges and chromosome aberrations in human and syrian hamster cell strains

Sister chromatid exchange (SCE) and chromosome aberration induction were determined for several inorganic metal salts. Arsenic, nickel, and beryllium salts at concentrations effective in causing transformation of Syrian hamster cells (HEC) induced SCE and chromosome aberrations of HEC and human lymphocytes, whereas sodium tungstate, a non-transforming chemical, neither induced SCE nor chromosome aberrations. Normal human and hamster cells exhibited equal sensitivity to SCE induction; nontoxic concentrations of sodium arsenite, beryllium sulfate, and nickel sulfate caused an increase of 8–10 SCE/cell over control values. Sodium arsenite, a trivalent arsenic, and sodium arsenate, a pentavalent arsenic, produced increases in SCE but the former was effective at lower concentrations. Both arsenic salts were less efficient in inducing SCE in human whole blood than in purified lymphocyte cultures. Sodium arsenite, sodium arsenate, nickel sulfate, and beryllium sulfate also caused damage consisting primarily of chromatid type of aberrations. In HEC, with doses most effective in SCE induction, all four metals produced aberrations in 16–21% of cells. In human lymphocytes, 34 and 30% of the cells had chromosome damage after sodium arsenite and sodium arsenate, respectively, whereas beryllium sulfate or nickel sulfate caused damage in about 10% of the cells. The induction of SCE and chromosomal aberrations by metals reemphasizes the sensitivity of cytological assays and their importance for detecting genetic damage caused by carcinogens.     

Sister chromatid exchanges and chromosomal aberrations induced by mitomycin C in mouse lymphocytes carrying a leukemogenic virus

The induction of chromosomal damage (sister chromatid exchanges (SCEs), chromosomal aberrations, and micronuclei) in T lymphocytes from mouse spleen was analyzed after treatment in vivo with different concentrations of mitomycin C (MMC). Lymphocytes were derived from BALB/Mo mice, which carry an endogenous type C retrovirus (Moloney murine leukemia virus, M-MuLV), and from BALB/c mice (controls, M-MuLV-free). Chromosomal damage was determined in vitro on lymphocytes stimulated with concanavalin A (Con A) and incubated for two generation cycles with bromodeoxyuridine (BUdR). The baseline frequency of SCEs was significantly higher in untreated BALB/Mo than in BALB/c lymphocytes. The frequencies of SCEs were significantly increased by increasing doses of MMC in both BALB/c and BALB/Mo T lymphocytes. Treatment with a low dose of MMC (0.3 mg/kg) produced an additive effect on SCE frequency in BALB/Mo lymphocytes, which was gradually suppressed by increasing the MMC concentration (3-5 mg/kg). Indeed, the levels of SCEs became significantly lower in BALB/Mo than in BALB/c lymphocytes at the highest MMC concentration tested (10 mg/kg), indicating that a negative synergistic effect was eventually produced. Chromosomal aberrations (breaks and total aberrations) were significantly increased by the highest MMC doses (5-10 mg/kg) and were more frequent in BALB/Mo than in BALB/c lymphocytes at 10 mg/kg MMC. The frequencies of micronuclei were increased by all MMC doses and were significantly higher in BALB/Mo than in BALB/c lymphocytes at 10 mg/kg MMC. These results are referred to interferences of M-MuLV and MMC with the function of enzymes, such as DNA topoisomerases, involved in the mechanism of SCE production.     

Evaluation of chromosomal aberrations, micronuclei, and sister chromatid exchanges in hospital workers chronically exposed to ionizing radiation.

Cytogenetic analysis was performed in peripheral blood lymphocytes from hospital workers chronically exposed to ionizing radiation in comparison to matched non-exposed individuals. The accumulated absorbed doses calculated for the radiation workers ranged from 9.5 to 209.4 mSv. The endpoints used were chromosomal aberrations (CA), micronuclei (MN), and sister chromatid exchanges (SCE). The frequencies of CA/100 cells observed for the exposed group were significantly (P=0.018) higher than in the control group: 3.2 and 2.6, respectively. Similarly, the mean numbers of SCE per cell were statistically higher (P=0.025) in the exposed group (6.2) in comparison with the control group (5.8). In the case of micronuclei analysis, no significant (P=0,06) difference between both groups was found, but these data should be cautiously interpreted since an increase in the frequencies of MN was found for radiation workers (3.0 MN/100 cells), compared to the control group (2.6 MN/100 cells) and this increase occur in parallel to CA and SCE frequencies. The difference between the results could be explained by the nature of CA and MN generation. The increased frequencies of CA and SCE in radiation workers indicate the cumulative effect of low-level chronic exposure to ionizing radiation, and the relevance of conducting cytogenetic analysis in parallel to physical dosimetry in the working place.     

Sister chromatid exchanges, chromosome aberrations and micronuclei in female lymphocytes: correlations with biological rhythms, miscarriages and contraceptive pill use

Our study looked at the variation in peripheral blood lymphocytes, during the menstrual cycle, of frequencies of sister chromatid exchanges (SCE) and micronuclei (MN) in 819 women and cells with aberrant chromosomes (CA) in a selected sample of 136 volunteers. We observed significant fluctuations in SCE and CA frequencies: SCEs reached a maximum value at the end of menstruation and a low at the time of ovulation, whereas CAs showed a continuous increase from the beginning of the menstrual cycle up to the time of ovulation and a progressive decrease thereafter. MN frequency did not fluctuate in a statistically significant way. No statistically significant differences in SCE, CA and MN frequencies were observed when fertile women were compared with women taking the contraceptive pill or those in menopause and no difference was found between women who had undergone physiological or surgically induced menopause. Moreover, no difference was found between women with a history of miscarriages and matched controls. These data together suggest that the natural variations in sexual hormone levels, but not those due to the contraceptive pill or their reduction at menopause, can contribute in modulating the baseline frequencies of SCEs and CAs. Moreover, these data suggest that the increased risks either of producing a chromosome imbalance in the progeny (eliciting miscarriages) or of occurrence of gynaecological diseases is not predictable by evaluating cytogenetic end-points in peripheral blood lymphocytes.