Sister Chromatid Exchanges In Lymphocytes Research Articles

Nitrate contamination of drinking water: evaluation of genotoxic risk in human populations.

Nitrate contamination of drinking water implies a genotoxic risk to man due to the endogenous formation of carcinogenic N-nitroso compounds from nitrate-derived nitrite. Thus far, epidemiological studies have presented conflicting results on the relation of drinking water nitrate levels with gastric cancer incidence. This uncertainty becomes of relevance in view of the steadily increasing nitrate levels in regular drinking water supplies. In an attempt to apply genetic biomarker analysis to improve the basis for risk assessment with respect to drinking water nitrate contamination, this study evaluates peripheral lymphocyte chromosomal damage in human populations exposed to low, medium, and high drinking water nitrate levels, the latter being present in private water wells. It is shown that nitrate contamination of drinking water causes dose-dependent increases in nitrate body load as monitored by 24-hr urinary nitrate excretion in female volunteers, but this appears not to be associated with peripheral lymphocyte sister chromatid exchange frequencies.

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.

Sister chromatid exchange in lymphocytes of patients with cancer of the larynx

The frequency of sister chromatid exchange (SCE) was studied in cultured peripheral lymphocytes from 15 untreated patients with carcinoma of the larynx and 10 healthy control subjects. Bromodeoxyuridine-incorporated chromosomes were treated with Hoechst 33258 and stained according to conventional methods. To measure SCE frequency, at least 15 mitoses per donor were evaluated. The SCE values were found to be higher in cancer cases than in control cases.

Sister chromatid exchanges in lymphocytes of nurses handling antineoplastic drugs

The effects of handling antineoplastic drugs were examined in a group of 23 nurses working in the hematology and oncology departments of different university hospitals in Ankara and in a group of 50 unexposed controls. The cytogenetic repercussions of exposure were assessed by examining sister chromatid exchanges (SCEs) in circulating lymphocytes which result from the breakage and rejoining of DNA at apparently homologous sites on the 2 chromatids of a single chromosome. A significant increased frequency of SCE is observed in nurses in daily contact with antineoplastics ( n = 23, mean SCEs/cell ± SE 6.5 ± 0.2) as compared to a group of controls ( n = 50, mean SCEs/cell 5.2 ± 0.2). The nurses who smoked also had a higher SCE frequency ( n = 15, mean SCEs/cell 7.0 ± 0.3) than non-smokers, ( n = 8, mean SCEs/cell 5.5 ± 0.3). A significant increase ( P < 0.001) in the mean number of SCE was found for non-smoking nurses as compared to non-smoking controls ( n = 27, mean SCEs/cell 4.1 ± 0.2).

Adriamycin-induced sister chromatid exchange and chromosomal aberrations in Down's syndrome lymphocytes

Blood samples from six Down's syndrome (DS) and six age- and sex-matched controls were cultured for 72 h in the presence of BrdUrd. Lymphocytes were then analysed at their second mitosis for sister chromatid exchange (SCE) and at their first mitosis for chromosome aberrations. Treatment with adriamycin (30 and 60 ng) showed a significant increase in frequency of SCE and chromosome aberrations in DS lymphocytes compared to normal lymphocytes at initiation of culture. Cells treated with adriamycin (ADR) for the last 24 h also showed a significant increase in SCE in DS lymphocytes compared to normal lymphocytes. A significant increase in chromatid-type aberrations was also recorded in DS lymphocytes after both treatments cultured for the last 24 h.

Increased frequency of sister chromatid exchanges in the peripheral lymphocytes of cigarette smokers

The incidence of sister chromatid exchanges (SCEs) in the peripheral lymphocytes of 23 smokers was significantly higher than that in 27 non-smokers (6.5 ± 0.3 compared with 4.1 ± 0.2 per cell, mean ± SEM). Both the duration of smoking and the number of cigarettes smoked per day appeared to influence SCE frequency. Significantly higher frequencies of SCEs were observed in those who smoked more than 10 cigarettes per day than in those who smoked less than 10 cigarettes per day. The frequency of SCEs in those who had habitually smoked for over 10 years was significantly greater than that in those who had smoked for less than 10 years.

Monitoring the exposure of rats to benzo[a]pyrene by the determination of mutagenic activity in excreta, chromosome aberrations and sister chromatid exchanges in peripheral blood cells, and DNA adducts in peripheral blood lymphocytes and liver

The relative sensitivity of various methods suitable for monitoring the exposure to genotoxicants was studied in rats treated orally by gavage with benzo[a]pyrene (BP). The results were related to the occurrence of DNA adducts in liver. Male Wistar rats were treated once by gavage, BP doses ranging from 1 to 200 mg/kg body wt. The monitoring methods applied were: (i) mutagenicity in urine and extracts of faeces (Ames test, Salmonella typhimurium TA 100), (ii) chromosome aberrations (CA) and sister chromatid exchange (SCE) in peripheral blood lymphocytes (PBL), and (iii) DNA-adduct formation in PBL and liver (32P-postlabelling method). Mutagens in faeces and urine were detectable from dose levels of 1 and 10 mg/kg body wt respectively. Maximum mutagen levels were found in faeces (direct and indirect acting) collected 0-24 h after treatment and in urine (direct and indirect acting, glucuronidated and non-glucuronidated) collected 24-48 h after treatment. DNA-adduct formation was apparent in PBL at 10 mg (one spot) and 100 mg (two spots), and in liver at 100 mg/kg body wt (two spots). At the latter dose, the total BP-DNA adduct level in PBL was twice as high as in liver. The major adduct in PBL showed location and elution characteristics of the BP-adduct bound to N2 of doxyguanosine (BP-dG). None of the adducts in liver could be identified as BP-dG. A slight increase in SCE was seen in PBL only at 200 mg/kg body wt 6 h after treatment. CA did not increase at any of the dose levels used. Our results show that in vivo exposure of rats to BP can be detected by analysis of mutagenic activity in excreta and DNA-adducts in PBL. In contrast, measurement of CA and SCE in PBL appeared to be a rather insensitive method for detection of BP exposure.

Cytogenetic analysis of peripheral blood lymphocytes in workers occupationally exposed to polychlorinated biphenyls

The ability of polychlorinated biphenyls (PCBs) to induce chromosome aberrations and sister chromatid exchanges (SCE) in peripheral lymphocytes was studied in a group of workers occupationally exposed to PCBs during the production of the Czechoslovak PCB products Delor 103 and Delor 106. The effect of PCB exposure was compared between an exposed group (N = 32, 3.25 +/- 0.34% aberrant cells, AB.C.), control group 1 (N = 20, 1.30 +/- 0.29% AB.C.), and control group 2 (N = 20, 1.60 +/- 0.31% AB.C.). The length of PCB exposure over 10 yr increased the frequency of AB.C. in a group exposed for 11-15 yr to 3.40% (N = 5) and in a group exposed for 16-25 yr to 5.85% (N = 7) vs. an increase of 1.60% AB.C. in group C2 and of SCE to 12.6 +/- 0.9/cell vs. 6.9 +/- 0.7 SCE/cell in C2. The clastogenic activity observed in this group may be the result of a high PCB concentration in blood plasma (320 +/- 190 micrograms PCB/l), and it is probably related to its solubility in adipose tissue, when it may act as another mutagen and carcinogen biotransformation inducer.

Frequency of sister chromatid exchange in peripheral lymphocytes of male pesticide applicators

In the present study 61 male pesticide applicators who worked in cotton fields and regularly sprayed pesticides such as DDT, BHC, endosulfan, malathion, methyl parathion, phosphamidon, dimethoate, monocrotophos, quinalphos fenvelrate, and cypermethrin were analyzed for sister chromatid exchanges, mitotic index, and cell cycle kinetics in peripheral lymphocytes. Subjects who handled pesticides were non-smokers and teetotalers and the data were compared with the matched control group. Statistical analysis revealed that the frequency of sister chromatid exchanges was significantly higher among the pesticide applicators at all the durations of exposure when compared to controls. Subjects exposed to pesticides also showed cell cycle delay and decrease in mitotic index when compared to the control group.

Evaluation of the mutagenicity of β‐myrcene in mammalian cells in vitro

The genotoxicity of the terpene beta-myrcene was evaluated in mammalian cells in vitro. Myrcene is the major constituent of oil of bay and hop which are used in the manufacture of alcoholic beverages. Myrcene is also present in lemon grass (Cymbopogon citratus), a plant widely used in Brazilian folk medicine. Recently, it was shown that myrcene is a very potent analgesic substance and might be an alternative to the already available analgesic drugs. Myrcene was tested up to 1,000 micrograms/ml (limit of solubility) in the presence and absence of S9-mix and did not induce chromosome aberrations and sister chromatid exchanges (SCEs) in human lymphocytes in vitro. Neither the mitotic index nor the proliferation index was influenced by the myrcene treatment. Myrcene did not cause increased mutation frequencies at the hprt-locus in V79-cells. Tests with and without S9-mix revealed negative results. There was no indication for induced cytotoxicity. However, myrcene reduced the SCE-inducing effect of cyclophosphamide in human lymphocytes in a dose dependent manner and also reduced the toxic and mutagenic effect of cyclophosphamide in V79-cells. Under the same test conditions, SCE induction by ethyl methanesulfonate (EMS) and benzo [a]pyrene (BP) was not significantly influenced by simultaneous myrcene treatment. The in vitro results show that myrcene is not mutagenic in mammalian cells, but has antimutagenic properties. The possibility that myrcene exerts its antimutagenic activity by inhibiting certain forms of the cytochrome P-450 isoenzymes required for activation of premutagens and precarcinogenes is discussed.

Lack of induced increase in sister chromatid exchanges in human lymphocytes exposed to in vivo therapeutic ultrasound

In 1984 Stella et al. reported that each of 10 patients exposed to therapeutic ultrasound had a statistically significant increase in sister chromatid exchanges (SCEs) at mid- and end of therapy; there was a wide range of clinical symptoms (e.g., elbow epicondylitis to knee arthrosis) in this set of patients. In the present study, a set of 4 patients each with some diagnosis recommending therapeutic ultrasound was similarly tested for SCE induction; an additional set of 4 healthy persons underwent sham-therapeutic ultrasound exposures. For both sets of subjects (patients, nonpatients) there was no increase in the frequency of SCEs.

Lymphocyte Proliferation and Sister Chromatid Exchange in Alzheimer's Disease

Sister chromatid exchange (SCE) and lymphocyte proliferation were studied in peripheral lymphocyte cultures derived from 5 patients with Alzheimer disease (AD), 5 control elderly subjects and 5 young donors. These parameters did not differ significantly between the AD group and the elderly control group, but higher SCE frequency and less intensive proliferation were observed in the AD group and in the elderly control group when compared to the young donors.

Sister chromatid exchanges in peripheral lymphocytes of urinary tract infection treated with nitrofurantoin

Nitrofurantoin, a widely used antibacterial agent in the therapy of urinary tract infections of bacterial origin, has been widely discussed in recent years due to its genotoxicity. Sister chromatid exchanges (SCE) were studied in lymphocyte cultures of 15 urinary tract infection patients before and after medication with daily oral doses of 10 mg/kg or 400 mg nitrofurantoin for 10 days. Both stages exhibited similar average numbers of SCE in circulating lymphocytes. The number of SCE was larger in smokers. The results of this study suggest that the short-term exposure to nitrofurantoin does not cause detectable cytogenetic abnormalities.

Chromosomal aberrations in patients with primary biliary cirrhosis

Chromosomal aberrations in untreated lymphocyte cultures, bleomycin (BLM)-induced aberrations and sister chromatid exchanges (SCE) in the peripheral blood lymphocytes of 11 patients suffering from primary biliary cirrhosis (PBC) and 14 matched control individuals were analysed. The lymphocytes of the PBC patients had on average a lower mitotic index (2.3) compared with controls (3.5) in the untreated cultures. The mean baseline rate of aberrations of the cultured lymphocytes of the patients was 5.3 aberrations per 100 metaphases (%); this was significantly different (P = 0.0291) from that of the controls with a mean of 2.3%. In lymphocytes of the patients and controls, most of the aberrations observed took the form of gaps; there was an almost equal breakage rate in both groups (0.5% and 0.4%, respectively). The average number of mitoses with aberrations in the PBC patients studied was double that of the controls (4.9% and 2.3% respectively, P = 0.0323). The mean number of the BLM-induced aberrations was 54.0% and 27.7% for the lymphocytes of the patients and controls, respectively. The mean number of the aberrant mitoses in the BLM cultures was 6 times higher than that of the untreated cultures for both groups, 25.7% and 14.6% respectively (P = 0.018). The chromosomal distribution of baseline and induced aberrations was not random. The PBC patients had a mean number of 8.7 SCE per mitosis, which was significantly higher than the SCEs in the controls (6.3 SCE per mitosis; P = 0.0156). The evidence suggests that the chromosomes of the lymphocytes of PBC patients may be less stable than those of the control individuals in this study.

Cytogenetic monitoring of chemical workers in production of the drug 1-propoxy-2-acetamino-4-nitrobenzol with reference to their smoking habits

The induction of chromosome aberrations (CAs) and sister-chromatid exchanges (SCEs) was examined in cultured lymphocytes from 23 individuals employed in the production of the drug 1-propoxy-2-acetamino-4-nitrobenzol. Lymphocytes of workers were cultured before and 13 weeks after starting professional activity. The latter showed a significant increase in both CAs and SCEs. Smokers (11 individuals) and non-smokers (12 individuals) were indistinguishable with respect to the frequencies of CAs or SCEs before starting professional activity, 13 weeks later smokers exhibited significantly more SCEs than non-smokers. This strongly suggests a comutagenic interaction of cigarette smoke and exposure to chemicals during drug production. On the basis of the technology applied the compound inducing CAs and SCEs in lymphocytes of smoking workers seems to be 2-acetamino-4-nitrophenol.

Sister-chromatid exchanges in lymphocytes from styrene-exposed boat builders

Sister-chromatid exchanges (SCE) were measured in peripheral blood lymphocytes from 40 workers in the boat-building trade. Twenty of these workers were exposed to significant amounts of styrene. The mean air concentration of styrene in the breathing zone of the boat builders was 209 mg/m 3 in the 7 exposed current smokers and 230 mg/m 3 in the 13 exposed non-smokers. Urinary styrene metabolites were also measured and the mean mandelic acid/creatinine ratios in the exposed, smokers was 275 mg/g, and in the exposed, non-smokers 323 mg/g. The SCE frequency in lymphocytes from the styrene-exposed group did not differ from that in the controls, although smoking significantly induced SCE in these workers.

Chromosomal aberrations and sister-chromatid exchanges in lymphocytes of workers exposed to sulphur dioxide

The frequencies of chromosomal aberrations and sister-chromatid exchanges (SCE) in peripheral blood lymphocytes of 40 workers chronically exposed to sulphur dioxide (SO 2) at a sulphuric acid factory in Taiyuan City (North China), were studied. It was shown that the mean frequency of chromosomal aberrations and the mean frequency of lymphocytes with chromosomal aberrations of the SO 2-exposed workers were both higher than the controls. The mean per 1000 metaphase frequencies of severe chromosomal aberration types (chromosome rings, translocations, and dicentrics) of the workers and the controls were 9.63 and 2.27, respectively. The difference between them was statistically significant ( p<0.01). It was also shown that the mean SCEs/cell of SO 2-exposed workers and non-exposed controls were 6.72± 0.22/cell and 2.71± 0.13/cell ( p<0.01) respectively. SCEs/cell in 39 workers were all higher than 5, only 1 worker was 4.73, However, 41 controls were all lower than 4, only 1 control was 4.92. The difference between the worker and the control group was statistically significant. These results show that SO 2 is a clastogenic and genotoxic agent. No positive correlation between the frequencies of chromosomal aberrations or SCE and length of service in the workers has been observed. No significant difference between smokers and non-smokers was found in these assays.

Sister chromatid exchange and proliferation pattern in lymphocytes from newborns, elderly subjects and in premature aging syndromes

Sister chromatid exchange (SCE) frequency and cell proliferation were examined in lymphocyte cultures from a group of newborns, a group of elderly subjects and from patients with syndromes who exhibit progeriform characteristics (progeria, Cockayne syndrome, Rothmund-Thomson syndrome and Christ-Siemens-Touraine syndrome) by using the bromodeoxyuridine incorporation differential staining technique. We observed a significantly increase in basal SCE frequency and a less intensive cell proliferation in cultures from elderly subjects than from newborns, as shown by the significant increase in percentage of cells in first generation simultaneous with a reduction of cells in more advanced generations. Lymphocyte cultures from each one of the patients studied also showed a decreased cell proliferation in relation to their respective control and to newborn cultures. Each of these syndromes showed higher baseline SCE levels than the control and than the newborn and elderly groups. Only the patient with progeria showed values similar to those for the elderly group. Thus, in addition to showing clinical characteristics similar to those observed during the normal aging process, these progeriform syndromes also show cytogenetic characteristics similar to those of older individuals.

Comparison of DNA adducts and sister chromatid exchange in lung cancer cases and controls : Perera F, Mayer J, Jaretzki A et al. Division of Environmental Sciences, Columbia University School of Public Health, New York, NY 10032. Cancer Res 1989;49:4446-51

In a molecular epidemiological study of lung cancer cases (n = 81) and noncancer controls (n = 67), polycyclic aromatic hydrocarbon (PAH)-DNA adducts were evaluated in peripheral blood leukocytes from all subjects and in a smaller number of lung tissue specimens collected prior to or at surgery. Sister chromatid exchanges (SCE) in lymphocytes were also studied in a subset of cases and controls. Questionnaire, medical record, or tumor registry data provided a family history of cancer, as well as information on cigarette smoking, dietary and occupational exposure to PAHs, and other factors related to SCEs. In both cases and controls PAH-DNA adducts in leukocytes measured by an enzyme-linked immunosorbent assay were not significantly related to age, sex, ethnicity, amount of cigarette smoking, passive smoking, dietary charcoal, or caffeine consumption. Nor did family history of cancer or histological type of cancer significantly affect adduct levels. However, when subjects were stratified by smoking status (current, former, and nonsmoker), lung cancer cases who were current smokers had significantly higher levels of covalent adducts than current smoker controls. A seasonal variation was observed in PAH-DNA binding, with a peak in adduct levels during July-October. This peak corresponds to that seen in a prior study of aryl hydrocarbon hydroxylase inducibility by other investigators. The finding of significant levels of PAH-DNA adducts in former smokers and non-smokers supports an earlier observation that this marker is not smoking specific but reflects a pervasive and variable "background" exposure to PAH. These results are consistent with a genetically determined enhancement of PAH-DNA adduct formation in leukocytes of lung cancer cases which is evident in current smokers. The results in lung tissue are limited by the small number of samples. Adduct levels were not significantly increased in lung tissue of smokers compared with nonsmokers. An inverse linear correlation was seen between adduct values in lung tissue and age of the donors. SCEs were significantly related to pack years of smoking. However, there was no difference in the frequency of SCE between cases and controls; nor were SCE and DNA adducts significantly correlated in this small sample.

Observation on the Frequency of Sister Chromatid Exchanges in the Peripheral Blood Lymphocytes of Healthy Old Women with Taichiquan Exercise

The frequency of sister chromatid exchanges (SCE) in the peripheral blood lymphocytes of eighteen healthy old women with 88 style Taichiquan exercise was studied. When compared with eighteen old women without exercise, the training group showed a decreased frequency of SCE in cultured peripheral blood lymphocytes at resting conditions. It is assumed that long term Taichiquan exercise provokes beneficial effects on lymphocytic chromosomes in the elderly.