Malignant melanoma: sister chromatid exchange analysis in three families

Sister chromatid exchange (SCE) was analyzed in stimulated lymphocytes and skin fibroblasts in members of three families with cutaneous malignant melanoma (CMM). Two of these families were characterized by familial CMM; the other family had one patient affected by CMM and two others with other cutaneous melanocytic lesions. All the patients had undergone surgery but no chemotherapy. Higher and differing SCE rates were found in lymphocytes and in fibroblasts of all patients. A wide range of SCE distribution was found in patients with high SCE rate. A few healthy close relatives also showed relatively high SCE rates and wide range distributions. These subjects may be regarded as a subset of family members at high risk for developing cancer. The variability of SCE rates and distribution may reflect genetic heterogeneity of CMM.     

广西大厂锡矿区职工外周血淋巴细胞姐妹染色单体交换(SCE)频率、染色体畸变率和微核率的观察

本文分析了38例大厂矿井下矿工、40例井上工作人员和27例非矿区正常人的外周血淋巴细胞SCE频率、染色体畸变率和微核率差异情况,发现井下矿工的SCE频率和染色体畸变率显著高于井上工作人员及非矿区正常人,微核率的差异无显著意义(P>0.05)。结合矿区肺癌流行病学调查结果对比分析,认为井下矿工长期接触的生产性粉尘中可能存在一些致癌物质,导致机体细胞遗传物质受到一定程度损伤。     

Evaluation of sister chromatid exchange as an indicator of sensitivity to N-ethyl-N-nitrosourea-induced carcinogenesis in rats

Sister chromatid exchange (SCE) frequencies in peripheral lymphocytes are a frequently used endpoint to indicate exposures to genotoxins in groups of humans. The aim of this study was to ascertain, in an experimental design, whether or not SCE rates have any association with the risk of cancer at the individual level in rats exposed to a known carcinogen. Individual SCE rates were determined in three consecutive analyses in cultured blood lymphocytes of 50 adult male Wistar rats. Analyses were done before as well as 24 hr and 7 days after a single intraperitoneal administration of 0, 25, 50, or 75 mg/kg of N-ethyl-N-nitrosourea (ENU). The animals were followed until death; also, the relationship between SCEs and carcinogenic outcome, i.e., the presence or absence of tumors, and their latency period were examined. ENU significantly decreased the life expectancy of the rats. The tumor types most clearly associated with ENU treatment were various gliomas and thyroid-gland and testicular tumors. ENU induced a moderate (maximally 1.6-fold) increase in the mean frequency of SCEs/cell at both sampling times after treatment. The effect was somewhat more pronounced 1 day rather than 1 week after treatment. The mean SCE rates in rats with ENU-specific cancers or in animals with early or multiple tumors did not differ from those in animals that survived no less than 65 weeks or longer without developing tumors. In ENU-treated animals with tumors, no relationship was found between the mean SCE rate and survival time. It is concluded that in outbred Wistar rats the SCE response in cultured lymphocytes does not indicate individual susceptibility to the carcinogenic action of ENU. On a group basis, however, animals with high SCE rates were shown to have increased risk of cancer.     

Tissue-specific induction of sister chromatid exchanges by ethyl carbamate in mice

Sister chromatid exchange (SCE) techniques were used to analyze the genetic effects of ethyl carbamate (urethane) in cultured mouse-bone marrow cells, and in several different mouse tissues in vivo. Ethyl carbamate concentrations up to 5.0 mg/ml were ineffective in causing a significant elevation of SCE in vitro. After in vivo drug administration, bone marrow, liver and spermatogonial cells all revealed significant dose-related increases in SCE. Baseline and relative incremental levels of SCE were somatic vs germ tissue-specific. Regenerating liver cells exhibited significantly greater absolute SCE values than all other tissues examined. Marrow cells revealed intermediate values, while germ cells were the least sensitive in SCE responsiveness. Spermatogonia required a fourfold higher dose, over that effective in somatic tissues, to promote an approximate doubling of the baseline SCE level. In vivo SCE analysis affords sensitive risk assessments for different tissues. Thus, this approach should be generally useful for studying compounds with questionable mutagenic potential, and/or those exerting target organ specificities of related biological activity (eg, toxicity, carcinogenesis).     

Sister chromatid exchange in aplastic anemia

The incidence of sister chromatid exchanges (SCE) in the lymphocytes of patients with aplastic anemia (AA) was determined before and after exposure to mitomycin C (MMC). The “baseline” SCE rate was significantly higher in AA, but MMC-induced SCE rate was not different compared to controls. It is suggested that some patients with AA may have an underlying DNA damage.     

Enhancement of SCE frequency by alpha-naphthoflavone in cultured lymphocytes in relation to environmental factors

One hundred and nine healthy subjects living in an urban area of Tuscany were monitored using sister chromatid exchange (SCE) analysis on lymphocytes cultured in standard or alpha-naphthoflavone (ANF)-supplemented medium in order to collect the most complete data possible for those constitutional and environmental factors with which genotoxic risk can be associated. ANF genotoxicity depends on its metabolic activation by cellular P-450 monooxygenase systems whose activity can be modulated by exposure to carcinogenic but nongenotoxic xenobiotics. Lymphocytes grown in standard conditions showed a significant increase of SCE frequency associated with smoking habits and age. Although the addition of ANF caused an upward shift of SCE frequency in all subjects, smokers, coffee drinkers, and blue-collar workers showed a significantly higher SCE level; this suggests that potential risk factors rising from a modified cell metabolism are present in these categories. These results indicate that in vitro ANF treatment of lymphocytes could be a useful tool in the detection of environmental exposure to those classes of chemicals involved in metabolic activation of promutagens. © 1995 Wiley-Liss, Inc.     

Spontaneous and 3-aminobenzamide-induced sister-chromatid exchange frequencies estimated by ring chromosome analysis

Ring chromosomes offer an opportunity to measure sisterchromatidexchange (SCE) frequencies without the use of an agent to differentiatesister chromatids: SCE frequencies can be determined from thenumber of dicentric rings formed in cells from a cell line carryinga monocentric ring chromosome. Ash is a pseudotetraploid Chinesehamster ovary cell line in which 40% of metaphase cells havea large ring chromosome. We have used this cell line to investigatethe spontaneous rate of SCE by determining the rate of dicentricring formation and have compared this with the rate of lossof the ring chromosomes over time. In the absence of both [³H]thymidineand bromodeoxyuridine, the spontaneous rate of SCE in Ash cellswas 0.12 SCEs/ring/cell cycle; this rate was increased by bromodeoxyuridine,by the polyfunctional alkylating agent mitomycin C, and by thepoly(ADP-ribose) polymerase inhibitor 3-aminobenzamide. Thisindicates that spontaneous SCE occurs in this line and thatnot all 3-amino-benzamide-induced SCEs are dependent upon incorporatedbromodeoxyuridine. Ring chromosomes were not lost over timeas rapidly as predicted by the SCE frequencies observed. Non-disjunctionof the dicentric ring, or anaphase bridge breakage followedby reunion to form one or two monocentric rings, are the mostlikely explanations for this discrepancy. ¹To whom correspondence should be addressed     

Sister chromatid exchange with and without in vitro mutagen induction in cultured skin fibroblasts from patients with adenomatosis of the colon and rectum

Fibroblast cell strains were obtained from skin biopsies taken from patients with adenomatosis of the colon and rectum (ACR), and their relatives. A total of 50 different fibroblast strains were tested for their frequencies of sister chromatid exchange (SCE) in vitro. These strains included nine from patients with the Gardner syndrome, 21 from patients with non-Gardner ACR, and 20 cell strains from healthy relatives who were not at an increased risk for ACR. In 23 strains, the SCE frequencies after in vitro exposure to N-methyl-N'-nitro-N-nitroso-guanidine (MNNG) were also determined. Both with and without MNNG induction, SCE values in the Gardner strains were found to be significantly higher than in the control strains (p less than 0.02 and p less than 0.03, respectively). Non-Gardner ACR strains differed only slightly from controls, thus making the difference between the control group and the pooled Gardner + non-Gardner ACR group not significant. In all groups, there was a significant increase in SCE after MNNG exposure, and those strains which had low SCE values spontaneously, also tended to have relatively moderate SCE values after MNNG induction. There was no significant difference between the ratios of SCE values with and without MNNG exposure in the different groups.     

Sister chromatid exchanges in leukemic patients

Sister chromatid exchange (SCE) was studied in PHA-stimulated peripheral blood lymphocytes from 36 newly diagnosed and untreated leukemic patients: 16 with acute lymphoblastic leukemia (ALL), 10 with acute nonlymphocytic leukemia (ANLL), and 10 with chronic myelocytic leukemia (CML). The metaphases analyzed show no chromosomal abnormalities. The mean SCE frequency (mean +/- SE) for each group of patients was: 6.8 +/- 0.4, 6.6 +/- 0.3, and 7.0 +/- 0.6 per mitosis, respectively, which was significantly lower than the mean SCE score for 30 controls (8.7 +/- 0.2). No differences in SCE score among ALL, ANLL, and CML and a similar SCE frequency by chromosome number and group allowed consolidation of all the cases into a single group of 36 leukemic patients (6.8 +/- 0.3). When the frequency of SCE was compared by chromosome number and group between the leukemic patients with the control group, a significant decrease in SCE frequency was observed due to a low SCE score in almost all the complements, except chromosome #1. It is suggested that the low SCE rate is related to the leukemic process itself.     

中药对再障染色体损伤的修复作用

目的　观察中药对由再生障碍性贫血 (AA)引起的染色体损伤的修复作用和对机体免疫功能的改善情况。方法　通过AA患者服用SB前后SCE率的变化和淋巴细胞转化的差别 ,观察生白片对再障患者遗传物质的保护和促进淋巴细胞转化作用。结果　AA患者在服用SB前的SCE值显著高于正常对照的P <0 .0 5 ) ,服用SB后SCE值显著降低 (P <0 .0 5 ) ;淋巴细胞转化率 (cpm)在服药前后也有显著差异(P>0 .0 5 ) 。结论　①AA患者具有染色体不稳定性 ,SB对AA的染色体不稳定性具有明显的修复作用 ;②SCE和淋巴细胞转化率可作为观察指标来研究中药的疗效机理。     

The effect of aging on sister chromatid exchange.

The advent of the bromodeoxyuridine(BrdU)-differential staining techniques has greatly facilitated the detection of sister chromatid exchanges (SCE). These SCE have been demonstrated to be an accurate reflection of DNA damage both in vitro in cultured cells and in vivo in mouse and rate bone marrow and spleen cells. In this review, we examine the effect of cellular aging on both baseline and mutagen-induced SCE levels. In all systems examined, aging did not appear to significantly affect the baseline levels of SCE. However, in human fibroblast cultures we have found a significant decrease in the levels of mutagen-induced SCE as a function of both in vitro passage level (in vitro aging) and the age of the cell culture donor (in vivo aging). In addition we have found a similar decrease in mutagen-induced SCE levels in both mouse and rat bone marrow cells and mouse spleen cells where examinations were performed entirely in vivo. Diminished mutagen-induced SCE levels were obtained with a wide variety of agents including mitomycin-C, cyclophosphamide, adriamycin, ethyl methanesulfonate and N-acetyl-2-acetoxyamino-fluorene. These decreased SCE levels were accompanied by increased frequencies of chromosomal aberrations in the older cell populations. If SCE represents a form of DNA repair as has been suggested by several investigators, our finding would indicate impaired DNA repair occurring in old cells.     

Increased cardiac contractility in acute uremia: interrelationships with hypertension.

To study the effects of acute uremia on the inotropic state of the rat heart, we subjected rats to bilateral nephrectomy and studied their hearts in the open chest 24 h later. Uremic rats had significantly higher systolic blood pressure than sham-operated animals. Left ventricular systolic pressure and maximum dP/dt, both during ejection and isovolumic contrations, were higher for any given end-diastolic pressure in hearts of uremic rats than in sham-operated animals. This difference in performance charcteristics was not abolished by doses of propranolol that blocked the heart rate response to isoproterenol. The administration of phenoxybenzamine during the 24 h of uremia abolished the blood pressure rise in uremic rats, but the increased contractile state persisted. Treatment of sham-operated animals with methoxamine to produce the same course of blood pressure as observed in uremic rats was also associated with an increased inotropic state. These results indicate that in the rat, acute uremia is associated with an increased inotropic state that is not mediated by beta-adrenergic mechanisms. The systolic hypertension of acute uremia is not the major cause of the increased contractility, although systolic hypertension without uremia can mimic the performance characteristics found in hearts of uremic rats.     

Sister chromatid exchanges in patients with carcinoma in situ of cervix uteri.

Sister chromatid exchange (SCE) was analyzed in lymphocytes of 21 patients with carcinoma in situ of cervix uteri and 19 control subjects. The mean SCE frequencies were 8.92 +/- 0.31 (n = 417) and 6.94 +/- 0.23, (n = 375) per metaphase in patients and controls, respectively. The increase of SCE levels in cancer patients was highly significant in respect to controls (p less than 0.001). Together with data of other authors in patients with precancerous and cancerous lesions of the cervix, our results suggest that there is no correlation between SCE rate and severity of cancerous lesions.     

A comparison of induced sister chromatid exchange levels in Chinese hamster ovary cells and cultured human lymphocytes

Human lymphocytes and Chinese hamster ovary cells were exposed to DNA damaging agents for two cell cycles, and the induced sister chromatid exchange (SCE) rate was compared. CHO cells showed a significant increase in SCE following treatment with bleomycin and vincristine whereas human lymphocytes did not. Both CHO cells and lymphocytes showed an increase in SCE with 5-bromodeoxyuridine (BrdUrd) and tritiated uridine (3H-Urd) but the increase was greater in CHO cells. SCE levels were similar after exposure to proflavine and colcemid did not increase the exchange frequency in either cell type. Apparently CHO cells are more sensitive than human lymphocytes to the actions of bleomycin, vincristine, BrdUrd, and 3H-Urd. SCE analysis in response to mutagens and carcinogens should therefore be based on more than one cell type.     

Sister chromatid exchange in dyskeratosis congenita lymphocytes.

Sister chromatid exchange (SCE) frequency in chromosomes from lymphocytes of a patient with dyskeratosis congenita was 12-2 per mitosis. Our 33 normal controls had a mean of 5-4 SCE per mitosis and 5 patients with Fanconi's anaemia averaged 7-6 SCE per mitosis. The rate of chromosome breakage was only 0-5% in the dyskeratosis congenita patient and 0 to 2-5% in controls, while the Fanconi's anaemia patients showed higher values.     

Sister chromatid exchanges in lymphocytes of patients with oral carcinoma

Sister chromatid exchanges (SCEs) were studied in cultured peripheral lymphocytes of 22 untreated patients with squamous cell carcinoma of the oral cavity and 29 age- and sex-matched controls. The SCE rate in cancer patients was not significantly higher compared with that found in controls, but there was a significant correlation between the SCE rate in lymphocytes of the cancer patients and the size of the primary tumor.     

Chromosome aberration and sister chromatid exchange in workers of the iron and steel factory of Iskenderun,Turkey

The aim of this study was to investigate, by using chromosome aberration (CA) and sister chromatid exchange (SCE) tests, whether or not the workers employed in the Iskenderun (Turkey) iron and steel factory have any genotoxic risk. The CA and the SCE were investigated in 48 males employed in a coke ovens unit and 8 males employed in a product side unit of the factory and in control groups. The frequency of CA was higher while the frequency of the SCE was not in all the smoker-nonsmoker workers than in smoker-nonsmoker control groups. In addition, there was no significant decrease in the RI, while the MI was significantly lower than in the controls. .     

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。     

Sister chromatid exchange in malignant lymphomas

Sister chromatid exchange (SCE) was evaluated in peripheral lymphocytes from 20 untreated patients with malignant lymphomas: 6 with Hodgkin's disease (HD), 14 with non-Hodgkin lymphoma (NHL), and 5 with lymphadenitis. The mean SCE frequency (+/- SE) was: 11.2 +/- 0.6, 11.0 +/- 0.6, and 7.2 +/- 0.3 for HD, NHL, and lymphadenitis patients, respectively, and 8.7 +/- 0.2 for the control group. No differences in SCE score were observed in HD and NHL. These results allowed us to consider both groups (HD and NHL) as a single neoplastic population (mean +/- SE, 11.0 +/- 0.4). No significant differences were found between the lymphadenitis and control groups. On the other hand, significantly higher SCE scores were seen in neoplastic populations than in the control and lymphadenitis groups (p less than 0.001 and p less than 0.01, respectively). When SCE was compared by chromosome number and group between neoplastic patients and controls, a higher SCE frequency was observed in chromosomes #1, #2, #3, and B, C + X, E, F chromosome groups than in controls. SCE levels were significantly higher in lymphoma patients in all chromosome numbers and groups mentioned than in patients with lymphadenitis. It is suggested that the high SCE rate in the malignant lymphoma population is possibly related to an increased chromosomal instability.     

尿毒症患者巨细胞病毒感染及与输血关系的研究

应用间接酶联免疫吸附试验法检测５２例尿毒症患者血清中巨细胞病毒特异性ＩｇＭ，ＩｇＡ抗体。结果表明特异性ＩｇＭ，ＩｇＡ抗体阳性率分别为６９．６％和１３．８％，明显高出对照组人群，统计学处理Ｐ〈０．０１，差异非常显著。