Sister chromatid exchange in lymphocytes from patients with malignant lymphoma

Summary Sister chromatid exchange (SCE) frequencies were studied in differentially stained lymphocytes from 47 patients with malignant lymphoma. Thirteen patients were untreated when studied. The mean SCE frequency [±standard error (SE)] for these patients was 12.7±0.9 per mitosis. The mean score for 40 controls was 6.1±0.3. SCE mean scores were significantly higher in the untreated patients than in the controls (P<0.001). Seven patients were treated with radiotherapy alone. They demonstrated a mean SCE frequency (8.8±0.8) significantly lower (P<0.01) than that found in untreated patients. Eleven patients received cyclophosphamide within 4 weeks prior to study. They demonstrated a mean SCE frequency (14.3±1.3) significantly higher (P<0.05) than that found in patients who had received regimens that did not contain cyclophosphamide in the prior 4 weeks (11.1±1.3) or who had been off drugs for at least 8 weeks (10.1±0.8). Our data suggest that untreated patients with malignant lymphoma have elevated SCE frequencies, which may be further increased by certain chemotherapeutic agents.     

Sister chromatid exchange in patients with viral disease

Sister chromatid exchange (SCE) frequencies were studied in differentially stained chromosomes from lymphocytes of 17 patients with viral disease. The mean SCE score for the patients was 8.7 +/- 2.9 standard deviations. SCE scores were significantly elevated in the patients compared with the controls (p less than 0.01); however, variability in SCE means was observed in the patients. SCE elevations were also present in long term cultured Epstein Barr virus positive human B lymphocytes.     

Sister chromatid exchange in lymphocytes from patients with Acute lymphoblastic leukemia

Summary Sister chromatid exchange (SCE) frequencies were studied in peripheral lymphocytes from 16 patients with newly diagnosed acute lymphoblastic leukemia (ALL) prior to the initiation of chemotherapy. The mean SCE frequency ( ±SE) for these patients was 12.2±0.2 per metaphase, which was significantly higher (P(0.001) than the mean SCE score for 14 agematched controls, 7.6±0.2. Five of these patients were studied again while they were receiving maintenance therapy consisting primarily of daily 6-mercaptopurine and weekly methotrexate. Their remission SCE levels remained significantly higher than controls (P(0.005). In addition, SCE levels were studied in 7 long-term survivors of ALL. Three of these patients had been receiving continuous maintenance therapy for at least 3 years. Their mean SCE scores were significantly greater than controls (P(0.005). The other 4 patients had finished their final course of chemotherapy at least 8 months prior to the time of sampling, and their mean SCE scores were not significantly different from controls (P>0.10). These data indicate that untreated patients with ALL have increased SCE levels which remain elevated during periods of remission maintained with chemotherapy. However, longterm survivors of ALL who are in remission and off chemotherapy do not demonstrate significantly increased SCE frequencies.     

Sister chromatid exchange in newborns

Summary Siter chromatid exchanges (SCE) were analyzed in the cord and postnatal blood of controlled groups of low and high birth weight infants to detect possible associations between abnormal birth weight and SCE frequency. Structural chromosome aberration rates had previously been evaluated for all infants, and possible correlations between aberration and SCE rates were sought.No correlation was found between neonatal or postnatal SCE frequency and birthweight, nor was there evidence of association of chromosome aberration rates with SCE frequency. In all groups of infants, however, mean postnatal SCE frequencies were significantly lower than mean neonatal SCE frequencies.     

Sister chromatid exchange in cell lines from malignant lymphomas (lymphoma lines)

Summary The frequency of sister chromatid exchanges (SCEs) was studied in cells from three freshly established lymphoma lines, derived from two patients with Hodgkin's disease and one patient with non-Hodgkin lymphoma. These values were compared to SCE rates found in cells from two long-established lymphoma lines (Raji and BJAB) and to those recorded in control cell lines of normal human donors. The highest SCE levels were demonstrated in the freshly established lymphoma lines, the lowest SCE values separated the lymphoblastoid cell lines from healthy controls, and the older lymphoma lines Raji and BJAB presented rates in between. The influences of BUDR concentration and of the duration of BUDR treatment on the frequency of SCEs were tested. Furthermore, the dependence of the SCE rate on the time interval between establishment of the cell line and its SCE investigation was considered. The connection between elevated SCE rates and the neoplastic nature of lymphoma lines is discussed.     

Sister chromatid exchange in cigarette smokers

Summary The incidence of sister chromatid exchanges in smokers and nonsmokers was investigated. There was no difference in the SCE rate between smokers and nonsmokers, nor was there any difference between heavy (>10 per day) and light (<10 per day) smokers.     

Sister chromatid exchange in immature haemopoietic cells,T-and B-lymphocytes

Summary Human lymphocytes from 18 healthy adults were cultured in minimal essential medium without folic acid. The addition of 4mM cytidine or 1 mM guanosine to cultures 24h prior to harvest produced a statistically significant increase in hot point 3p14 breaks. An excess of 3mM adenosine or thymidine had no such effect on the hot point. The mechanism of the effects of nucleosides on hot points was discussed.     

Sister chromatid exchange in human chromosomes from normal individuals and patients with ataxia telangiectasia.

A new fluorescence plus Giemsa staining technique now makes the detection of sister-chromatid exchange (SCE) a relatively easy matter in cells containing 5-BrdU-substituted DNA. The technique has been applied to human cells to examine the distribution of SCE between different people and within different chromosomes. The results show: (1) That there were no large differences in the incidence of SCE between blood leukocyte chromosomes from male and female adults and newborn, and that similar frequencies were found in cells from two patients with ataxia telangiectasia which, nevertheless, showed the typical increases in chromosomal aberrations. (2) The distribution of SCE between chromosomes in the complement was found to be proportional to chromosome length, although the smaller chromosomes were under-represented, but not significantly so. (3) The distribution of SCE within chromosomes was nonrandom, with a deficiency in the centromeric and an excess in the mid-arm regions. There was no evidence for an excess of SCE in chromosome regions rich in AT DNA sequences. (4) The frequency of SCE is to some extent dependent of 5-BrdU concentration, but the influence of concentration is minimal within the range of from 1 to 160 muM. Human cells exposed over two cell cycles at these higher BrdU levels have around 14 SCE per cell-a frequency virtually identical with that observed in cultured cells from the Chinese hamster, wallaby, and rat kangaroo.     

Sister chromatid exchange frequencies in Progeria and Werner syndrome patients.

An analysis of the baseline and mitomycin-C-induced sister chromatid exchange (SCE) frequencies in peripheral lymphocytes derived from three patients with progeria and three Werner syndrome patients is presented. SCE frequencies did not differ significantly between the two groups of patients and their normal controls.     

Sister chromatid exchange in lymphocytes in myelodysplastic syndrome

Sister chromatid exchange (SCE), percentage of first, second, third mitoses, blastic transformation index and mitotic index in patients with myelodysplastic syndrome (MDS) (3 with refractory anaemia, 2 with refractory anaemia with sideroblasts, 1 with refractory anaemia with excess of blasts, 4 with refractory anaemia with excess of blasts in transformation) and in 15 healthy volunteers were estimated. Three types of lymphocytes cultures were set up: first with phytohemaglutinin (PHA), second with PHA and bromodeoxyuridine (BRdU), third with BRdU. In healthy persons the SCE frequency was negatively correlated to proliferating rate index, but in MDS such correlation was not found. The lymphocytes cell cycle duration based on percentage of mitoses was longer in MDS patients than in controls. The results of our studies show the disturbances of lymphocytes during cell cycle division resulting in higher SCE frequency and lower proliferating rate compared to controls.     

Sister chromatid exchange induced by anti-herpes drugs.

The rate of sister chromatid exchange induced by several anti-herpes agents was measured to assess their potential mutagenicity. The agents--5-iodo-deoxyuridine (IDU), 5-trifluoromethyl-deoxyuridine (TFT), and [E]-5-(2-bromovinyl)-deoxyuridine (BVDU)--were incubated at various concentrations with human lymphocytes and fibroblasts, and that rate of sister chromatid exchanges was measured. In lymphocytes and fibroblasts BVDU and IDU did not induce exchange except at concentrations of 50 mg/l, while TFT increased the rate of exchange at a concentration of 0.5 mg/l. The rate of sister chromatid exchange is a sensitive index of chromosomal damage, and these findings provide information on the safety of some of the antiherpes agents tested. TFT increased the rate of exchange at a concentration that coincides with its minimal antiviral concentration, but BVDU did not induce exchange at therapeutic concentrations.     

Sister chromatid exchange in the centromere and centromeric area

Central and peripheral sister chromatid exchanges (SCE) were evaluated separately in human phytohemagglutinin (PHA)-stimulated lymphocytes after culture for 72 h in 5-bromodeoxyuridine (BrdU) containing medium. At the same time, the length of chromosome No. 1 was measured in 10 metaphases per case and the mean value taken as a representative parameter for the contraction of chromosomes. The statistical analysis of regression revealed a close relationship between the percentage of SCE observed in the centromere and the contraction state of chromosomes (P less than or equal to 0.01). A statistically significant increase of central exchanges was seen in more condensed chromosomes, due to the difficulty in differentiating clearly between centric and pericentric exchanges. Consequently, if exchanges in the centromere are omitted from evaluation, this would lead to spuriously low SCE rates in more contracted chromosomes. In order to exclude the variable factor of chromosome contraction in SCE studies, we highly recommend inclusion of counts of central exchanges. Results obtained on chromosomes with twisted chromatids, a situation which tends to stimulate SCE, should be omitted.     

Sister and non-sister chromatid U-type exchange in rye meiosis

Aberrant meiotic chromosome configurations in an experimental population of rye lines are known to result from spontaneous U-type exchanges during meiotic prophase. Both sister chromatid and non-sister chromatid exchanges occur and this study is concerned with the relative frequencies of sister and non-sister exchanges. The anaphase I observations reveal a marked excess of non-sister U-type exchange configurations and it is argued that this reflects an original excess of prophase non-sister U-type exchanges. This conclusion is discussed with special reference to the origin of meiotic U-type exchanges and their relation to regular crossover exchanges.     

Sister chromatid exchanges and chromosome aberrations in fibroblasts from patients with retinoblastoma

Summary The frequencies of sister chromatid exchanges (SCEs) and chromosome breaks were investigated in five diploid fibroblast strains derived from three patients with deletion 13[del(13)] retinoblastoma, one patient with a hereditary form of retinoblastoma, and one trisomy 13. The fibroblasts with del(13)(q14q22) showed slightly increased SCEs (at a P level of 5–10%), but the others, including del(13)(q12q14), the hereditary form of retinoblastoma, and trisomy 13, did not have increased SCEs as compared to normal controls. No increase in chromosome breaks was found in these fibroblasts. The results suggest that retinoblastoma is not associated with spontaneous increased chromosomal instability.