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.     

Sister chromatid exchanges in patients with retinoblastoma

Spontaneous and mitomycin C(MMC)-induced sisyer chromatid exchanges were studied in 11 patients with retinoblastoma and 7 normal controls. Spontaneous rates were similar in patients and in controls. The MMC-induced rate was found to be significantly higher in bilaterally affected patients than in controls. It is suggested that this increase may be due to a DNA repair deficiency. However, it is not possible to clarify wether this abnormality is associated with the retinoblastoma gene or with another factor acting on the degree of expressivity of the disease in gene carriers.     

Sister chromatid exchanges in patients with oral submucous fibrosis

The incidence of sister chromatid exchange (SCE) was investigated in the lymphocyte chromosomes of 45 patients with oral submucous fibrosis and 56 age- and sex-matched nonsmoking controls. The frequency of SCE was 9.26 +/- 2.15 in patients with oral submucous fibrosis, which was significantly higher than the mean SCE value of 5.49 +/- 1.24 observed in normal controls. The frequency of SCE in patients with oral submucous fibrosis addicted to the habit of betel with tobacco chewing, "bidi"/cigarette smoking and combined habits of chewing and smoking of tobacco were 8.12 +/- 1.69, 9.43 +/- 1.87, and 10.06 +/- 2.28, respectively. These values were also significantly higher as compared with the SCE values observed in normal controls.     

Sister chromatid exchanges in adult epileptic patients on phenytoin therapy

Sister chromatid exchanges (SCE) were studied in lymphocyte cultures of 12 adult male epileptic patients on long-term monotherapy with phenytoin (PHT) and of matched controls. Significantly increased frequency of SCE was observed in the epileptic patients as a group and in almost all individuals, indicating a detectable chromosome damaging effect of PHT therapy on its human users.     

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.     

Sister chromatid exchanges in the lymphocytes of patients with oral leukoplakia

The incidence of sister chromatid exchange (SCE) was investigated in lymphocyte chromosomes of 59 patients with oral leukoplakia and 65 age- and sex-matched nonsmoking controls. The frequency of SCE was found to be 8.61 +/- 1.89 in patients with oral leukoplakia, which was significantly higher than the mean SCE value of 5.58 +/- 1.26 observed in normal controls. The frequency of SCE in patients with oral leukoplakia addicted to the single habit of betel with tobacco chewing, bidi/cigarette smoking, and combined habits of chewing and smoking of tobacco were found to be 7.95 +/- 1.63, 8.17 +/- 1.66, and 9.23 +/- 2.14, respectively. These values were also significantly higher as compared to the SCE values observed in normal controls.     

Sister chromatid exchanges and chromosome aberrations in rubber workers

Sister chromatid exchanges and chromosomal aberrations were studied in peripheral blood lymphocytes of 55 rubber workers (from two different plants) and 35 controls mainly employed in office jobs. In both plants an increased frequency of SCEs (P less than 0.05 for plant A and P less than 0.01 for plant B) was detected in nonsmoking rubber workers as compared with nonsmoking referents. When the SCEs of worker groups belonging to the different job categories were compared with referents, the only groups showing statistically significant increases in SCEs were the smoking workers from the weighing and mixing departments of factory A and the nonsmoking weighers of factory B. A slight increase in the SCE frequencies was seen especially among smoking workers employed in the chemical mixing departments. The frequency of structural chromosome aberrations was not significantly increased in the occupational groups studied, the only exception being the small group of nonsmoking weighers in plant B. Among both the exposed workers and the controls, smokers had a higher mean SCE frequency than nonsmoking referents. This difference was significant between the exposed smokers and nonsmokers of plant A (P less than 0.01) and between smoking and nonsmoking controls for plant B (P less than 0.001). In addition, the chromosome aberration frequency of smoking controls of plant A was significantly higher (P less than 0.01 when gaps excluded and P less than 0.05 when gaps included) than that of nonsmoking referents. Also, smokers among controls for plant B had an increased frequency of aberrations in their cultured blood lymphocytes when compared with nonsmokers. This difference was significant (P less than 0.05) when gaps were excluded.     

Sister chromatid exchanges and dementia of the Alzheimer type

Sister chromatid exchange (SCE) analysis was carried out on ten patients with the clinical diagnosis of dementia of the Alzheimer type (DAT) and 11 cognitively-intact controls of a comparable age. There was no significant difference between patient and control groups in either the mean baseline SCE frequency or the SCE frequency following in vitro exposure to mitomycin-C. The present results, based on the largest sample (n = 21) published to date, fail to confirm the single positive report in the literature of an increased baseline SCE frequency in DAT patients compared to controls.     

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.     

Metal ion release from fracture fixation devices: a potential marker of implant failure

Stainless steel is the alloy most frequently used for fracture fixation devices (FFD). We aimed to verify if the ion release evaluation could be a surrogate marker of performance and could allow an early detection of implant failure in patients with stainless steel FFD. We measured the nickel (Ni) and chromium (Cr) serum content in patients undergoing the retrieval of stainless steel plates (group I) or intramedullary nails (group II), because of consolidation or failure. Forty-five healthy donors were recruited as controls. Furthermore, the diagnostic performance of these values was evaluated: analysis power, sensitivity, specificity, positive and negative predictive values, likelihood ratios, and diagnostic accuracy were calculated. A significant increase of ion values was demonstrated in patients with failed plates, compared with the values recorded in patients with well-fixed plates (p = 0.002 for Cr and p = 0.002 for Ni), and in healthy subjects (p = 0.0002 for Cr and p = 0.003 for Ni). No significant difference was found between stable implants and controls (p = 0.8 for Cr and p = 0.06 for Ni). A high specificity (0.92 for Cr and 1.00 for Ni), positive predictive value (0.87 for Cr and 1.00 for Ni), and positive likelihood ratio (9.10 for Cr) were calculated for ion testing in plates. The substantial metal content elevations in patients with plates and the positive likelihood ratio above 5 for chromium testing suggest that ion dosage may be a useful surrogate marker for the presence of malfunctioning of these devices, perhaps before the onset of clinical and radiographic changes.     

Sister chromatid exchanges in cells defective in mismatch, post-replication and excision repair

Three processes associated with DNA damage and genomic instabilityhave been defined experimentally as operating during or soonafter DNA replication: mismatch repair, post-replication repairand sister chromatid exchange. All these processes appear tooperate on damage and/or errors in newly replicated DNA. Bothmismatch repair and post-replication repair involve resynthesisof up to 1 kb of newly synthesized DNA: mismatch repair operateson single-base or slippage errors; post-replication repair operateson persistent gaps in newly synthesized DNA caused by damageon parental strands. Using colon cancer cells with differentmismatch repair capacity, together with normal cells and excision-repair-defectiveand post-replication-repair-defective xeroderma pigmentosum(XP) cells, we analysed possible interactions between theseprocesses. No evidence for overlap of mismatch repair with excisionor post-replication repair was found. However, post-replication-repair-defectiveXP variant cells that were SV40 transformed showed higher UV-inducedsister chromatid exchange frequencies than did untransformedcells. This suggests that sister chromatid exchanges in theXP variant are closely involved with UV-induced replicationerrors that are enhanced by transformation. ¹To whom correspondence should be addressed     

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.     

Sister chromatid exchanges at different times after repeated injections of thiophosphamidein vivo

The frequency of sister chromatid exchanges in rabbit peripheral blood lymphocytes was estimated after three intravenous injections of thiophosphamide in doses of 0.5 and 2 mg/kg body weight at 2-week intervals. It is demonstrated that 24 h after the first injection the frequency is significantly higher than after subsequent injections. Translated fromByulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 123, No. 1, pp. 73–74, January, 1997     

Sister chromatid exchanges in peripheral lymphocytes from women with carcinoma of the uterine cervix

Sister chromatid exchanges (SCE) are reciprocal exchanges between sister chromatids. It has been reported that in patients with cervical cancer, the frequency of SCE in peripheral lymphocytes is significantly higher than that in normal individuals; however, other studies have shown no significant difference. The aim of this unmatched case-control study was to compare the mean number of SCE per metaphase in lymphocytes from women with and without carcinoma of the cervix uteri. The SCE specimens were prepared by the fluorescence plus giemsa technique in peripheral lymphocytes from 28 women with carcinoma of cervix uteri and 28 controls. The mean number of SCE per metaphase in women with carcinoma of cervix uteri (7.80 +/- 1.05) was higher than the control group (6.98 +/- 1.13) (P < 0.05; t-test). This study had a statistical power of 0.80 and an alpha value of 0.05. This finding suggests that an increased number of SCE in peripheral lymphocytes is associated with cervical cancer. We consider that the lack of reported association of SCE and cervical cancer might be attributed to the none determination of the statistical power and sample size.     

Sister chromatid exchanges induced by tertiary butyl hydroquinone in bone marrow cells of mice

Tertiary butyl hydroquinone (TBHQ)--a phenolic antioxidant, was evaluated by assessing the induction of sister chromatid exchanges (SCEs) in bone marrow metaphase cells of mice. Six concentrations, 0.5, 2, 20, 50, 100, and 200 mg/kg, of TBHQ were injected intraperitoneally. A positive dose-response effect in the SCE frequency was observed using the Cochran-Armitage trend test. Two mg/kg of TBHQ was found to be the minimum effective dose. Study of the cell-cycle kinetics showed a delay in cell cycle induced by the higher concentrations of TBHQ. Thus, TBHQ was found to be a DNA damage-inducing agent and also a cytotoxic chemical in vivo in mice.     

Sister chromatid exchange and chromosome abnormalities in uremic patients

Chronic renal failure heightens the risk of malignancy. We therefore examined lymphocytes from 44 uremic patients and 24 normal controls for chromosome abnormalities and sister chromatid exchange (SCE) rate. This is the first report of SCE in uremia. Uremia was found to increase structurally abnormal chromosomes and elevate the rate of SCE. These cytogenetic changes in uremia may play a role in the heightened risk of cancer.     

Sister chromatid exchanges in chick embryos after treatment with the phenoxy herbicide MCPA.

The phenoxyherbicide and peroxisome proliferator 2-methyl-4-chlorophenoxyacetic acid (MCPA) was tested for its ability to induce sister-chromatid exchanges (SCE) in chick embryos. Erbitox E30 (a commercial formulation containing 28% MCPA sodium potassium salt as active ingredient) was injected into the air chamber in concentrations of MCPA of 0, 0.35, 0.7, 1.4, 2.8, or 5.6 mg/egg on day 0 of incubation. Pure MCPA sodium salt was tested at 2.8 mg/egg. Neutral red at 0.25 mg/egg was the mutagenic reference compound (positive control group). Eggs were then incubated for 4 days. MCPA induced a slight but significant increase in SCE frequency (about 1.3 times base line) at 2.8 mg/egg. The dose of 5.6 mg/egg was toxic. No difference in genetic activity between the commercial formulation and the pure compound was found. A cell cycle delaying effect of MCPA was evident at all the dose levels tested. The mitotic index remained unchanged.     

Sister chromatid exchanges: A reexamination of the evidence for sex and race differences in humans

Published evidence for human sex and race differences in sister chromatid exchange (SCE) levels is reexamined. There is substantial support for the conclusion that women average approximately 0.5 SCE/cell higher than men among normal healthy adults. An index of heterogeneity for SCE counts for cells from a single subject is introduced, and this statistic is applied to the data of Butler [1981]. who compared Caucasians, Blacks, Native Americans, and Orientals with regard to SCE levels. There is evidence in Butler's data of differences in the heterogeneity index among these four racial groups, but this finding needs independent verification in a larger study.     

Sister chromatid exchange in cancer

Sister chromatid exchange (SCE) techniques have been shown to have great potential for use in the in vitro screening of suspected mutagens and carcinogens. Application of these techniques to bone marrow cells and/or lymphocytes from patients with various hematologic malignancies has demonstrated significant abnormalities in SCE frequencies in some of these diseases, as well as showing drug treatment effects. Interpretation of abnormal SCE findings in cancer patients is currently hindered by the lack of a clear understanding of the basic molecular and biochemical mechanisms involved in SCE formation. The potential practical use of SCE techniques in the diagnosis and treatment of cancer can not adequately be appreciated until this basic understanding is achieved.     

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.