Differences In Sister Chromatid Exchanges Research Articles

Cytogenetic damage in peripheral blood cultures of Chaetophractus villosus exposed in vivo to a glyphosate formulation (Roundup)

Different concentrations of a glyphosate formulation, Roundup® Full II (66.2% glyphosate) were tested in culture peripheral blood of armadillo Chaetophractus villosus with cytogenetic biomarkers like mitotic index (MI), chromosomal aberrations (CA), sister chromatid exchange (SCE) and cell proliferation kinetics (CPK) by means of replication index. Adults animals of both sexes were exposed to RU at four concentrations ranging from 0.026 mL RU solution to 0.379 mL RU daily in oral treatment with the same volume (0.2 mL) during 7 days. We analyzed the induced damage at different times considering T0 as control value, one (T1), seven (T7) and 30 days (T30). One day after, only the higher concentration shows MI significant differences (p < 0.05), at T7 the frequency increases and at T30 it decreases reaching T0 values. The analysis of CA frequencies shows that only 0.106 mL RU/day exhibit significant differences vs T0 values. A great variability is expressed in the values of standard deviation (SD) and in the wide confidence intervals of the media. One day after treatments (T1) all four concentrations shows significant differences in SCE vs T0 values. Replication Index (RI) does not show significant differences. The dose-response behavior was not observed in either CA or SCE. The consistency of the findings obtained with the same biomarkers in vitro support the idea of expanding studies in order to characterize the risk doses for these mammals.

Long-term monitoring of sister chromatid exchanges and micronucleus frequencies in pharmacy personnel occupationally exposed to cytostatic drugs.

Many antineoplastic drugs were found to have carcinogenic, mutagenic and teratogenic potential. The aim of this study was to carry out cytogenetic and internal dose monitoring of hospital pharmacy personnel regularly involved in the preparation of cytostatic agents, in order to test possible cytostatics-induced genotoxic effects due to occupational exposure under routine working conditions, and in cases of accidental contamination. Platinum in whole blood and anthracyclines in plasma were measured to assess internal exposure to cytostatics. The level of cytogenetic damage was determined in peripheral blood lymphocytes with the micronucleus test and the sister chromatid exchange assay. Five series of monitoring were performed over a period of 2 years. No significant differences in the mean frequencies of sister chromatid exchanges (SCE) and micronuclei (MN) were found between occupationally exposed probands and controls (9.9 +/- 1.4 vs 10.1 +/- 1.2 SCEs/cell and 21.2 +/- 7.2 vs 23.3 +/- 7.5 MN/2000 binucleated (BN) cells, n = 16). Significant elevations of SCE or MN were detected in seven out of 12 cases of accidental contamination at the workplace, whereas no increase in platinum in blood and anthracyclines in plasma was observed in these probands. Two cases of non-reported contamination were identified by measurement of epirubicin in plasma. Smoking was found to increase the SCE significantly. No correlation between individual SCE scores and MN scores was observed. Our findings support a transient increase in SCE or MN after relevant exposure to cytostatic drugs in cases of accidental contamination. The lack of significant differences in SCE and MN between hospital pharmacy personnel and unexposed controls, points to high standards of safety at the corresponding workplaces.

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.

Induction of sister chromatid exchanges in human peripheral blood lymphocytes by bromoform: investigation of the role of GSTT1-1 polymorphism

Brominated trihalomethanes (THMs) are disinfection by-products present frequently in chlorinated drinking water. Brominated THMs are mutagenic in a variety of systems and are carcinogenic in rodents. The metabolism of brominated THMs is thought to involve a GSH conjugation reaction leading either to formaldehyde or DNA-reactive intermediates via glutathione S-transferase-theta ( GSTT1-1), which is polymorphic in humans. In the present study, we have determined the genotoxicity of one of the brominated THMs, bromoform (BF), by measuring its ability to induce sister chromatid exchanges (SCEs) in whole-blood (WB) cultures of human peripheral blood lymphocytes from GSTT1-1+ and GSTT1-1− donors. The results showed no differences in SCEs per cell by BF between GSTT1-1+ and GSTT1-1− individuals when the cells were exposed to 5×10 −3 M BF at the beginning of cell culturing (10.8±0.85 vs. 10.57±0.47, respectively), at the 16th (9.66±0.91 vs. 9.57±0.07), or the 24th h (8.21±0.61 vs. 8.29±0.24) of cell growth. Although GSTT1-1 is expressed in the erythrocytes, the lack of expression of the GSTT1-1 gene in the target cells (lymphocytes) may account for this observation.

Low sensitivity of the sister chromatid exchange assay to detect the genotoxic effects of radioiodine therapy.

To assess the genotoxic risk associated with 131I therapy, sister chromatid exchanges (SCEs) and cells with unusually high SCE counts (HFC) were determined in a follow-up study performed with 46 hyperthyroidism and 39 thyroid cancer patients treated with 131I. In addition, a cross-sectional study was also carried out with 78 control persons and 51 thyroid cancer patients that had completed radioiodine therapy from 1 to 6 years prior to the current investigation. In the follow-up analysis, the study was conducted over time and four blood samples were drawn from each patient: the first one prior to the radioiodine treatment, with the remaining three taken sequentially over the year after therapy. Concerning the results obtained for the whole population in the follow-up study, the SCE and HFC values found after radioiodine therapy did not show any significant increase, neither in the hyperthyroidism nor thyroid cancer groups. Unlike the results mentioned above, when the effect of smoking habit was considered, there was a slight but significant increase in SCE in the samples taken 3 months and 1 week after 131I therapy in the hyperthyroidism and thyroid cancer non-smokers, respectively. The data obtained in the cross-sectional study did not show differences in SCE and HFC between the control group and the cancer group treated with 131I. It is noteworthy that among the different parameters analysed, smoking habit is the only factor that showed a direct relationship with SCE and HFC and, as a consequence, smokers had significantly more SCE and HFC than non-smokers. Taking into account our previous investigations showing a highly significant increase in the frequency of micronuclei for the same patients and sampling times, the outcomes obtained would suggest that the eventual genotoxic effect of 131I therapy could not be clearly detected by the SCE assay. This would reinforce the view that ionizing radiation appears to be a poor inducer of SCEs.

Assessment of sister chromatid exchange in mouse embryos produced by microsurgical fertilization.

The treatment of male factor-related infertility has been approached with the advent of several methods for microsurgical fertilization, such as the partial dissection of the zona pellucida (PZD) and the injection of sperm into the perivitelline space (PVSI) of oocytes. These techniques are designed to increase sperm-oolemma interaction by circumventing passage of the sperm through the zona pellucida. The present study was performed to evaluate the influence of PZD and PVSI on the in vitro development of mouse embryos by assessing the rate of sister chromatid exchange (SCE). SCE is considered to be a sensitive indirect indicator of DNA lesions due to various conditions. Oocytes were cultured in vitro after PZD or PVSI and then examined for SCE. There was no significant difference in SCE between control and treatment groups of embryos and the values were similar to those reported by Saito et al. (Fertil Steril 41:460-464, 1984). The rate of SCE was low during the first two mitotic cycles, then increased from cycle two to three before declining slightly between the 3rd and 4th cycles of cell division. These data demonstrate that the direct interaction of sperm and oocyte by PZD or PVSI did not have an adverse effect on the development of mouse embryos as assessed by the rate of SCE.

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.

A study of sister-chromatid exchange in peripheral lymphocytes of hepatitis B patients with HBsAg positive and their children

Previous studies of sister-chromatid exchange (SCE) in patients with hepatitis B have been reported. But as far as we know, no such work has been done in children born to parents with hepatitis B, either one or both of whom are infected. In the present study, frequencies of SCE in the peripheral lymphocytes of 30 hepatitis B parents with hepatitis B surface antigen (HBsAg) positive and 40 of their children were observed. SCE frequencies of 20 normal adults and 3 normal children were analysed for comparison with the patients and their children. The results obtained from all of the samples were as follows: (1) The hepatitis B patients with HBsAg positive had a significantly higher SCE frequency than the normal adults ( P<0.01); (2) the children born after their parents contracted hepatitis B had a significantly higher SCE frequency than normal children ( P<0.01); (3) there was no significant difference in SCE ( P>0.05) between children born after their parents contracted hepatitis B, children born after their mothers acquired it and children born after their fathers acquired it. The above results indicate that hepatitis B patients with HBsAg positive and their children born after they contracted hepatitis B had significantly higher frequencies of SCE; these data might throw new light on the study of genetic factors acting on the mechanism of hepatitis B.

In vitro SCE discrepancy between embryonic and extraembryonic mouse tissues

In vitro sister-chromatid exchange (SCE) background levels and cytokinetics were compared in embryonic (whole embryo cell suspensions) and extraembryonic (yolk sac and amnion, placenta) cells of inbred and outbred strains at various gestational stages (day 12–17). Results indicate a tissue origin (embryonal, extraembryonal) related variation in the formation of baseline SCE frequencies and cytokinetics. The significant higher SCE levels in extraembryonic tissues (maximum increase of 2 × the background values of the embryo cells) were independent of mouse strain and gestational stage. An average of 4–5 SCEs/cell in embryo cells is contrasted by 7–9 SCEs/cell in extraembryo cells. Mitotic index was generally lower and average generation time longer (by 2–3 h) in extraembryonic tissue cells. No significant differences in SCE frequencies and no changes in cytokinetics were detected at the BrdU concentrations used (1.2–4.8 μg/ml). The reason for the inter-tissue differences in baseline SCE is still not clear.

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.

Characterization of the distribution of sister chromatid exchange frequencies: implications for research design.

Mitoses from 21 individuals were examined to characterize the within and between subjects distributions of sister chromatid exchange (SCE) frequencies. The importance of accounting for both the within subjects and between subjects variability in the design and interpretation of research is demonstrated. A computer simulation study was performed to evaluate the estimate of an individual's mean SCE rate. A power analysis was performed using our transformed descriptive data to determine the percentage difference in SCE which could be detected between two groups (with 95% probability) as a function of both the number of mitoses per individual and the number of individuals in each group. Tables are provided as guidelines. Conclusions from our work include: (1) The empirical distribution of SCEs within an individual is best described by a negative binomial distribution; (2) The predominant source of variability in baseline SCE rates is between cells within a given individual rather than between individuals and can be accounted for in experiments by counting adequate numbers of mitoses per individual; and (3) There is a systematic relationship between the mean and SD for SCEs which should be removed prior to hypothesis testing by taking either a logarithmic transformation or square root transformation of the data.

Elevated sister chromatid exchange and cell cycle analysis in bone marrow in childhood ALL

Sister chromatid exchange (SCE) frequencies were analyzed in both stimulated and unstimulated bone marrow samples from eight patients recently found to have childhood acute lymphocytic leukemia (ALL). Six of the patients had elevated SCE frequencies in stimulated marrow when compared to control values. In unstimulated marrow, all four patients had elevated SCE frequencies. These data agree with peripheral leukocyte findings in ALL. Cell cycle analysis revealed no significant differences between the patient marrows and the control marrows. Since no correlation between cell cycle distribution and SCE frequency was found, it is suggested that the differences in SCE observed may be related to the type of proliferating cell.