Mean Sister Chromatid Exchange Frequency Research Articles

Sister chromatid exchanges in peripheral lymphocytes in newborns treated with phototherapy and vitamin E.

A study was undertaken to determine whether blue fluorescent light might affect the sister chromatid exchange (SCE) frequency of peripheral lymphocytes in icteric newborns undergoing continuous phototherapy treatment (72 h). Also, the potential preventive effect of vitamin E on SCE frequency was studied in a subgroup of 11 preterm and 9 fullterm newborns after daily administration of vitamin E (46.44 mumol/kg/d, im). The results revealed that only the preterm icteric newborns showed an increase in mean SCE frequency of peripheral lymphocytes after phototherapy (9%, p = 0.02), but in no case did the highest SCEs/cell ratio exceed the normal values. No correlation was found between the average SCE rate and birth weight, gestational age or bilirubin levels. Also, no difference in SCEs was observed between newborns treated or untreated with vitamin E.

Baseline frequency of sister-chromatid exchanges in 142 persons of the general Korean population

Baseline frequencies of sister-chromatid exchange (SCE) were measured in lymphocytes of 142 healthy Koreans ranging in age from newborn infants to the fifties. The overall mean frequency of SCE was 8.78±0.24/cell. However, highly significant differences were found between individuals. The mean SCE values of the newborn babies and small children less than 10 years old were significantly lower than those of other age groups. No age effect was, however, observed in adolescent and adult subjects. Females had statistically higher SCE levels than males. The mean SCE frequencies of smokers, measured in male subjects more than 10 years old, were slightly, but statistically significantly, higher than those of non-smokers.

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 < 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.

Sister chromatid exchange frequencies in a group of individuals with unfavorable reproductive health

Sister chromatid exchange (SCE) frequencies and other cytogenetic parameters were investigated in peripheral blood lymphocytes from 92 subjects comprising 44 parents of malformed offspring or repeated fetal wastage (Group I) and 48 controls, age and sex matched, having normal reproductive health (Group II). The karyotypes were normal and the mean mitotic indices were comparable in both groups. The mean frequency of SCE per metaphase in Group I (8.67 ± 0.32) was significantly higher than the mean for group II (6.65 ± 0.16), and the cellular replicative index in Group I (1.78 ± 0.04) was significantly different from that of Group II (1.66 ± 0.03). The results are discussed in the light of the present understanding of the etiology and mechanism of production of sister chromatid exchanges.

Sister chromatid exchange frequency in directly prepared cytotrophoblasts: Demonstration of in vivo deoxyribonucleic acid damage in pregnant women who smoke cigarettes

Assessing frequency of sister chromatid exchange is a sensitive method of monitoring exposure to clastogens, mutagens, and other substances that induce deoxyribonucleic acid damage. Aware that cigarette smoke is associated with increased sister chromatid exchange in many cell types, we sought to determine whether an in vivo effect of cigarette smoke could be demonstrated by study of sister chromatid exchange in chorionic villus cells. Directly prepared cytotrophoblasts and cultured mesenchymal core cells were analyzed. Mean sister chromatid exchange frequency in cytotrophoblasts from smoking subjects (8.87 sister chromatid exchanges per cell) was significantly greater than in nonsmoking subjects (5.81 sister chromatid exchanges per cell; p < 0.001); however, no significant difference in cultured mesenchymal core cells was found. Our results demonstrate that maternal exposure to cigarette smoke results in direct placental deoxyribonucleic damage, which in turn could explain deleterious effects of smoking on pregnancy. Increased sister chromatid exchange frequency was observed only in directly prepared cytotrophoblasts, showing the necessity of using this cell type to evaluate the effects of clastogens on placentas. (AM J OBSTET GYNECOL 1991;165:1877-80.)

Sister-chromatid exchanges in lymphocytes from infants with Down's syndrome

Sister-chromatid exchange (SCE) frequencies were studied in blood lymphocytes from 12 patients (3 females and 9 males) with Down's syndrome (DS). The mean frequency of SCE per metaphase for the patients (both sexes) was 9.2 ± 0.8 which was significantly higher ( P < 0.01) than the mean SCE value (5.1 ± 0.2) scored for 16 healthy infants (8 females and 8 males). A significant increase in the mean frequency of SCE in 12 parents of infants with DS (8.7 ± 0.9 SCE/cell) was noticeable when compared with 20 parents of normal infants (6.3 ± 0.1 SCE/cell). Increases in cellular division with reduction in their replication were also observed in patients with DS. Treatment with mitomycin C (0.05 μg/ml), hycanthone (0.1 μg/ml)_and γ-radiation (0.1 Gy) revealed a significant ( P < 0.01) increase in frequencies of SCE in DS lymphocytes and in those of their parents as compared to controls. These data may reveal a familial hypersensitivity reaction to these agents. The results indicate a genomic instability and deranged DNA-repair mechanisms which are accentuated by exposure to mutagenic agents, the underlying causal factor for which might be genetic.

Biclonal analysis of busulfan-induced sister chromatid exchange in blast crisis of Philadelphia chromosome-positive chronic myeloid leukemia

The frequency of induced sister chromatid exchange (SCE) as a sensitive parameter for chemotherapy resistance was studied after in vitro treatment with busulfan in four cases of myeloid blast crisis of Philadelphia chromosome (Ph)-positive chronic myeloid leukemia (CML). Prerequisite was a chromosomally biclonal condition with cells characterized by numerical and/or structural clonal evolution [e.g., +8, +17, +19, or i(17q)] and those only Ph +, which allowed a direct comparison of both clones. We found almost identical mean SCE frequencies in cells with and without clonal evolution after in vitro treatment with 1,3, and 5 μg busulfan. The distribution of the SCE frequency within chromosome groups also remained similar in all cases. Because the SCE assay has proven a very sensitive tool for detection of resistance to chemotherapy with alkylating agents, we conclude that the clonal evolution of CML blast crisis is not associated with a significant degree of chemotherapy resistance. Other aspects, e.g., the lack of normal bone marrow cells necessary for reconstitution of hematopoiesis, may play a more important role in the poor results of chemotherapy in myeloid CML blast crisis.

A genetic study of human interferon-α-induced repair of DNA damage in hepatitis B patients

In vitro treatment with human interferon-α (HuIFN-α) of hepatitis B virus-infected peripheral lymphocytes from 17 hepatitis B patients induced a decrease in the frequency of sister-chromatid exchanges (SCE). There was a significant difference in mean SCE frequencies between the HuIFN-α-treated patients and the control group, but not between acute and chronic hepatitis B patients treated with HuIFN-α

Sister chromatid exchange frequency in Hodgkin's disease patients with elevated in vivo hprt mutant frequencies

The frequency of sister chromatid exchanges (SCEs) was determined in Hodgkin's disease (HD) patients prior to therapy, following radiotherapy, and following combined radiotherapy and chemotherapy. The frequency of hprt- mutants in these patients has been reported previously. The frequency of SCEs and hprt- mutants in the same individuals were compared. In non-HD controls the mean SCE frequency and the mean of high SCE frequency cells (HFCs) were significantly increased by smoking, while mutant frequency (MF) showed no effect. Untreated HD patients had mean SCEs, mean HFCs and mean MFs that were higher than non-MD controls. In treated patients, mean SCE and HFC frequencies were lower than untreated patients and non-HD controls, while their MFs were significantly elevated. Overall, SCE frequency was not correlated with MF in control or HD patient groups, suggesting that these biomarkers may reflect, in this case, fundamental biological differences between these processes.

Chromosomal aberration and sister-chromatid exchange frequencies in peripheral blood lymphocytes of a large human population sample II. Extension of age range

We have previously reported on a cytogenetic-epidemiological study of chromosomal aberration and sister-chromatid exchange (SCE) frequencies in peripheral blood lymphocytes (PBL) of a cohort of 353 healthy employees of the Brookhaven National Laboratory (Bender et al., 1988). This sample has now been increased in order to extend the age range represented and, incidentally, the representation of non-white subjects. In total, the data now include chromosomal aberration information from 108 950 cells and SCE information from 25 397 cells from 613 samples from 493 subjects. Neither the mean frequencies of any of the chromosomal aberration types nor the mean frequency of SCE have changed notably through the addition of the new subjects and samples. The mean age at sampling of the population is now 43.1 years with a range of from 1.1 to 83.7 years. However, we still find no significant relationship of the frequency of any conventional aberration category to age with the single exception of the dicentric chromosome, which now shows a positive regression ( p = 0.001). The raw mean SCE frequencies show a statistically significant increase with subject age, but when cigarette smoking status is taken into account, no significant age relationship is found. As with the earlier samples, neither aberration nor SCE frequencies was influenced by race. Mean SCE frequencies, measured in non-smokers, were about 5% higher in females than males. Only one aberration category, “supernumerary acentric fragment”, was significantly related to sex. This “aberration”, known to constitue early centromere separation of an X chromosome, is much more common in females than in males and, in the females, increases significantly with increasing subject age.

Effect of hyperthermia on the frequency of sister-chromatid exchanges in patients with cancer of cervix uteri

The frequencies of sister-chromatid exchanges (SCE) were studied in patients with cancer of the cervix uteri and normal controls at 37°C and 40°C. At 37°C the mean frequency of SCE was found to be 8.26 ± 1.91 in untreated patients with cervical cancer and 7.91 ± 1.68 in cancer patients treated with radiotherapy; these values were significantly higher than the control value of 5.34 ± 1.28 exchanges. Increase of the growth temperature to 40°C elevated the SCE frequency to 11.95 ± 2.12 in patients without radiotherapy treatment, 13.37 ± 2.17 in patients with radiotherapy treatment and 7.82 ± 1.84 in normal controls. These data indicate that there is a differential induction of SCEs by hyperthermia in the lymphocytes of control women and patients with cancer of the cervix uteri.

SCE increases after an accidental acute inhalation exposure to EtO and recovery to normal after 2 years

Sister-chromatid exchanges (SCEs) were studied in 3 workers accidentally exposed for about half an hour to high levels of ethylene oxide (more than 700 ppm) during a sterilizing process. The 3 workers had clinical symptoms of exposure and were tested for SCE frequencies 5 days and 2 years after the accident: 2 had also been tested 6 months earlier. All 3 showed a similar increase in SCEs after the accident, to a mean of 13.8 SCEs/cell compared with 8.6 for a control group. The incidence of ‘high-frequency cells’ was markedly elevated but decreased over 2 years, when the mean SCE frequencies had also returned to pre-accident levels.

Paradoxical changes in SCE frequencies persistently elevated in vivo, on exposure to a mutagen in vitro

Lymphocyte cultures from 4 individuals with persistently significantly elevated frequencies of sister-chromatid exchange (SCE) were examined with no treatment, and with 2 concentrations of mitomycin C. In each of the 4 cases, the mean level of SCEs in the untreated lymphocytes exhibited a paradoxical reduction in SCE frequency when exposed to the lower (0.005 μg/ml) of the two doses of mitomycin C. At the second higher dose of mitomycin C (0.025 μg/ml) the mean level of SCE/cell exceeded the untreated mean. When the distributions of SCE/cell were examined it appeared that the untreated cultures had two or more populations of cells; one was in the normal SCE frequency range, while the second population was in an elevated SCE frequency range. The paradoxical reduction in SCE frequency was apparently due to elimination of, or mitotic inhibition of cells in the highest range of SCE frequency, while a small elevation in SCEs was initiated in the cells with a normal SCE frequency. Thus, mean levels of SCE/cell can be misleading. This data suggests that new exposure to the same or a different genotoxic agent might possibly result in a misleading lowering of the mean SCE frequency.

Sister chromatid exchanges in the lymphocytes of control women, pregnant women, and women taking oral contraceptives: Effects of cell culture temperature

The incidence of sister chromatid exchange (SCE) was investigated in the lymphocytes of control women, pregnant women, and women using oral contraceptives after culture at 37 degrees C and 40 degrees C. At 37 degrees C, the mean frequency of SCE (MEAN +/- S.E.) was found to be 7.91 +/- 0.30 in pregnant women and 8.53 +/- 0.29 in oral contraceptive users which were significantly higher than the SCE value of 5.56 +/- 0.21 found in control women. Increase in growth temperature to 40 degrees C elevated the SCE frequency to 11.86 +/- 0.44 in pregnant women, 12.76 +/- 0.46 in oral contraceptive users and 7.24 +/- 0.26 in control women. These data indicate that there is a differential induction of SCEs following increased cell culture temperature in the lymphocytes of pregnant women and oral contraceptive users, compared with control women.

Cadmium sulfate does not induce sister chromatid exchanges in human lymphocytes in vitro

Mutagenic properties of cadmium sulfate were analyzed by the method of sister chromatid exchanges (SCEs) in lymphocytes of human peripheral blood taken from 4 donors. No significant increase was found in the mean frequency of SCEs in lymphocytes exposed to 1.6 × 10 −3 mM, 3.1 × 10 −3 mM and 6.2 × 10 −3 mM CdSO 4 in culture.

CYTOGENETIC STUDIES ON BLOOD LYMPHOCYTES FROM PATIENTS WITH SCHISTOSOMA MANSONI

Chromosomal aberrations and sister chromatid exchange (SCE) frequencies were studied in peripheral blood lymphocytes from 10 patients with Schistosoma mansoni prior to initiation of chemotherapy. The mean frequencies of chromatid and chromosome breaks for the patients were 1.80 and 2.30%, respectively, which were significantly higher (P less than 0.01) than the means 0.35 and 0.30%, scored for 20 healthy controls. Significant increase in the mean frequency of SCEs in the patients (9.1 +/- 0.5 SCE/cell) was noticeable when compared with the controls (6.2 +/- 0.1 SCEs/cell). Reductions in the lymphocyte divisions and replications in the patients were also observed. These results indicate that infection with S. mansoni could have in vivo mutagenic effects on human chromosomes.

Variation in the human lymphocyte sister chromatid exchange frequency as a function of time: results of daily and twice-weekly sampling.

The variation in lymphocyte sister chromatid exchange (SCE) frequency was investigated in healthy nonsmokers who were not taking any medication. Two separate studies were undertaken. In the first, blood was drawn from four women twice a week for 8 weeks. These donors recorded the onset and termination of menstruation and times of illness. In the second study, blood was obtained from two women and two men for 5 consecutive days on two separate occasions initiated 14 days apart. One donor participated in both studies. Analysis of the mean SCE frequencies in each study indicated that significant temporal variation occurred in each donor, and that more variation occurred in the longer study. Some of the variation was found to be associated with the menstrual cycle. Peaks in the SCE frequency were observed at times that corresponded approximately to ovulation and to the beginning and end of menstruation. In the daily study, most of the variation appeared to be random, but occasional day-to-day changes occurred that were greater than those expected by chance. To determine how well a single SCE sample estimated the pooled mean for each donor in each study, we calculated the number of samples that encompassed that donor's pooled mean within 1 or more standard errors. For both studies, about 75% of the samples encompassed the pooled mean within 2 standard errors. An analysis of high-frequency cells (HFCs) was also undertaken. The results for each study indicate that the proportion of HFCs, compared with the use of Fisher's Exact test, is significantly more constant than the means, which were compared by using the t-test. These results coupled with our previous work suggest that HFC analysis may be the method of choice when analyzing data from human population studies.

Sister chromatid exchanges in garlic (Allium sativum L.) callus cells

A technique is described for differential staining of sister chromatids and the study of sister chromatid exchanges (SCEs) in garlic (Allium sativum L.) callus cells. BrdU incorporation into newly synthesized DNA was ensured by culturing calli on medium containing 100 μM BrdU+0.01 μM FudR+1 μM Urd. SCEs were visualized by FPG staining technique and their frequency was analysed. Mean frequency of SCEs in callus cells was higher than that in meristem root-tip cells. Using the same staining method, cell cycle time of callus cells was analysed. It was found that it ranges from 48 to 132 hrs. The method described represents a new approach in the study of genetic instability of plant cells cultured in vitro.

Studies on sister chromatid exchanges in patients with Hodgkin's disease

Sister chromatid exchange frequencies were analyzed in bone marrow cells and in stimulated peripheral blood lymphocytes from 20 patients with Hodgkin's disease. Sister chromatid exchange studies were also carried out in the bone marrow of eight and peripheral blood of 11 normal subjects separately. Among the patients, ten were newly diagnosed and ten patients were survivors who had received therapy 30–64 months prior to studies. The mean sister chromatid exchange frequencies in bone marrow and peripheral blood of untreated patients were 3.93 ± 0.7/cell and 4.09 ± 0.91/cell, respectively, which were not significantly different from those of normal subjects (3.22 ± 0.7/cell and 5.16 ± 1.3/cell in bone marrow and peripheral blood, respectively). The mean sister chromatid exchange frequencies in bone marrow and peripheral blood in five of the untreated patients 3–4 months after initial therapy and in a treated (30–64 months after therapy) group were close to the sister chromatid exchange values of the untreated group. Analysis of the distribution of exchanges per chromosome or chromosome groups showed a nonrandom distribution of exchanges in chromosomes #1, #2, and #3, and in E-, F-, and G-group chromosomes in the normal controls and in Hodgkin's disease patients.

Sister Chromatid Exchange in Garlic (Allium SativumL.) Meristem Root-Tip Cells

SUMMARYDifferential staining of sister chromatids by the fluorescent plus Giemsa (FPG) technique was performed in Allium sativum L. chromosomes unifilarly substituted with BudR. For this purpose optimal concentrations of FudR, BudR and Thd were determined and their influence was studied on cell cycle kinetics. The distribution of sister chromatid exchanges (SCEs) per chromosome was in good agreement with the expected Poisson distribution. There were statistically significant differences in mean SCEs frequencies per cell among respective plants tested. The mean frequency recorded was 99.78 SCEs per cell.