Comparison of baseline sister-chromatid exchanges (SCE), cyclophosphamide-, ethylnitrosourea (ENU)-induced SCE, ENU-induced cell-cycle delay and chromosome aberrations between Peru and laboratory mice

The baseline sister-chromatid exchange (SCE) frequency and sensitivity to the effects of the mutagens cyclophosphamide (CPP) and ethylnitrosourea (ENU) in bone-marrow cells of descendants of wild mice trapped from Rimac valley in Peru (Peru mice) were studied and compared to the same effects in laboratory mice. Baseline SCE of the Peru mice were significantly higher than those of the C57BL/6J and DBA/2 mice. The average SCE/cell of 4 Peru mice was 5.4 (range 3.8-7.6), while the average of SCE/cell of either 4 C57BL or 5 DBA mice was 3.2 (range 3.0-3.4). The variation of SCE/cell among Peru mice studied was statistically significant whereas among C57BL or DBA mice it was not. SCE frequencies of primary cultures derived from the ear tissue of 10 Peru (mean SCE/cell = 8.5) were also significantly higher than those of 6 C57BL mice (mean SCE/cell = 7.4). CPP treatment resulted in a dose-dependent increase of SCE frequencies in bone-marrow cells of all the mice. However, some of Peru mice treated with CPP had significantly higher SCE than the other Peru mice and than all of the C57BL and DBA mice treated with equivalent dose. ENU induced increased SCE frequencies in Peru and C57BL mice. Again some of Peru mice either had significantly higher SCE, greater extent induced cell-cycle delay or chromosome aberrations (CA) than other Peru mice and than of all the C57BL mice treated with equivalent dose.(ABSTRACT TRUNCATED AT 250 WORDS)     

Sister-chromatid exchanges in association with occupational exposure to ethylene oxide

Sister-chromatid exchange (SCE) frequencies in employees potentially exposed to ethylene oxide (ETO) were compared with those in unexposed control groups. Three worksites where the previous environmental control of ETO was known to have differed were chosen. Within these worksites, subjects were categorized into high potential exposed, low potential exposed and control groups. An additional community control group was obtained. Blood samples for chromosome studies of peripheral lymphocytes were drawn at several time points over a period of 24 months. The effects on SCE of age, sex, smoking habits and reader variation were considered. Worksites I, II and III, respectively, represented increasing levels of exposure. At Worksite III large differences among groups persisted over 24 months. At Worksite II, the SCEs in the high potential exposed workers were higher than those in the other groups. At no time was the low potential exposed group at Worksite II statistically significantly higher in mean SCE than the worksite controls. No consistent differences among groups were noted in Worksite I.     

Cytogenetic damage in workers exposed to ethylene oxide

Sister-chromatid exchanges (SECs) and chromosomal aberrations (CAs) were detected in the peripheral lymphocytes of 41 sanitary workers exposed to ethylene oxide (EO) in the sterilizing units of 8 hospitals in the Venice Region. The first group (19 workers) was exposed to 10.7 +/- 4.9 ppm EO, expressed as the time-weighted average concentration for an 8-h working day (TWA/8 h conc.), and the second group (22 workers) to 0.35 +/- 0.12 ppm. Each exposed worker was paired with a control of similar age and smoking habits. A highly significant (P less than 0.001) increase in the mean frequency of SCEs was found in the higher exposure group, 14 (74%) exposed subjects having significantly increased levels of SCEs compared to their matched controls. In the lower exposure group, the increase in mean frequency of SCEs was lower, though still significant (P less than 0.05): 7 (33%) exposed subjects had higher and 1 (5%) had a lower SCE level than the matched controls. From the first group, 10 subjects, 7 of whom had increased SCE levels, were reanalysed 12-18 months after their exposure had been lowered or interrupted: in only 2 of them the SCE level was significantly decreased. A statistically significant correlation between SCE frequency and level of EO exposure (TWA/8 h conc.), as well as a multiple correlation between SCE level and EO exposure, smoking and age were found. However, no interaction could be detected between EO exposure and smoking in the induction of SCEs. In controls, SCE frequency was correlated with smoking and age. In the higher exposure group, the number of both chromatid- and chromosome-type aberrations, independent of gaps, was significantly increased, whereas in the lower exposure group only the frequency of chromosome-type aberrations, excluding gaps, was statistically higher than in controls. The level of CAs remained to a great extent unchanged in the 10 subjects re-examined at a later stage after lowering or halting exposure. Taking the group as a whole, the frequency of cells with total CAs was found to be weakly (P = 0.05) correlated with EO exposure, and was not correlated with smoking, age or SCE frequency.     

Variations of SCE frequencies in peripheral lymphocytes of ex-smokers

We measured SCE frequencies over a period of 8 months in 14 smokers who stopped smoking at the start of the study. In a first group of 10 subjects, who did not resume smoking during the period of cytogenetic follow-up, a lowering of SCE frequencies was already evident after 18 days and this became statistically significant after 78 days. SCE decrease was related to the logarithm of the period (in days) for which smoking was interrupted (r = 0.98; p less than 0.001). In a second group of 4 subjects, who at various times resumed smoking, the decrease of SCE followed the same pattern as in the first group during the period of nonsmoking, but SCE frequencies rose even higher once smoking was resumed. Our study indicates that the decrease of SCE in ex-smokers is rather rapid during the first 78 days after stopping smoking, and much slower from the 78th to the 233rd day.     

Sister-chromatid exchange in cultured lymphocytes of ewes and their newborn lambs

The incidence of sister-chromatid exchange (SCE) in cultured lymphocytes of ewes and their newborn lambs was determined using the BrdU-Giemsa technique. In all ewe-lamb pairs, the SCE rate in the lambs was less than that of the ewes. The mean SCE frequencies per chromosome of the ewes after lambing and of the newborn lambs were 0.1909 and 0.1581, respectively. The statistical analysis shows that a significant difference exists between SCE in the adult female sheep and their lambs. At the same time, a negative correlation was observed between SCE rate and cell proliferation. The results of this study are compared with those of previous reports on age-dependency of SCE.     

Baseline frequency of sister-chromatid exchanges (SCE) in newborn lymphocytes and its relationship to in vivo aging in humans

Heparinised cord blood from newborns and peripheral venous blood from three other age groups of individuals (1-75 years) have been cultured in vitro to obtain baseline frequencies of SCE and to see if the frequency of baseline SCE in vitro varies as a function of aging in vivo. The results demonstrate an age-dependent variation in the frequency of SCEs. Although the SCE frequency was lowest (5.10/cell) in 1-5-year-old infants, a significantly higher (P less than 0.001) frequency (8.97/cell) was observed in the cord blood of newborns. In old age, the level of SCE also increased. The plausible reason(s) for such observations is discussed.     

Cytogenetic study of persons occupationally exposed to ethylene oxide.

Ten persons occupationally exposed to ethylene oxide (EO), used in the sterilization of medical instruments, were studied at a hospital. The estimated concentration to which they were exposed was 60-69 ppm, TWA. Peripheral blood samples from 10 workers and 10 controls of the same age and sex were taken to determine the frequency of sister-chromatid exchanges (SCE) and chromosomal aberrations (CA). The mean frequencies of SCE/cell (X = S) were 13.27 for the exposed workers and 6.05 for controls. Chromosome aberration frequencies in exposed individuals were significantly increased compared with controls. A significant relationship between the frequencies of SCE and CA and EO exposure was demonstrated. Blood chemistry parameters such as urea, creatinine, uric acid, lactic dehydrogenase, glutamic oxaloacetic and pyruvic transaminases, luteinizing gonadotropin and follicle stimulating gonadotropin and thyrotropin were also measured and found to be within the normal range.     

Cytogenetic study of persons occupationally exposed to ethylene oxide

Ten persons occupationally exposed to ethylene oxide (EO), used in the sterilization of medical instruments, were studied at a hospital. The estimated concentration to which they were exposed was 60–69 ppm, TWA. Peripheral blood samples from 10 workers and 10 controls of the same age and sex were taken to determine the frequency of sister-chromatid exchanges (SCE) and chromosomal aberrations (CA). The mean frequencies of SCE/cell (X = S) were 13.27 for the exposed workers and 6.05 for controls. Chromosome aberration frequencies in exposed individuals were significantly increased compared with controls. A significant relationship between the frequencies of SCE and CA and EO exposure was demonstrated. Blood chemistry parameters such as urea, creatinine, uric acid, lactic dehydrogenase, glutamic oxaloacetic and pyruvic transaminases, luteinizing gonadotropin and follicle stimulating gonadotropin and thyrotropin were also measured and found to be within the normal range.     

Sister-chromatid exchanges in lymphocytes of smokers in an experimental study

The frequency of sister-chromatid exchanges (SCEs) was studied in peripheral blood lymphocytes of 26 young male smokers and 10 non-smokers who had recently entered military service. The levels of SCEs were examined in 4 consecutive blood samples taken after short experimental periods of smoking only low-tar (LT) or medium-tar (MT) cigarettes. The incidence of SCEs was significantly higher in the the group of smokers than in the group of non-smokers. The SCE levels of the smokers were found to be associated with the personal smoking history; the observed increase in the SCE frequency correlated with the years of smoking measured as cumulative pack years. The difference in type of cigarette did not influence the SCE frequencies.     

The effect of valproic acid on SCE and chromosome aberrations in epileptic children

Sister-chromatid exchange (SCE) and chromosome aberrations have been studied in peripheral lymphocytes of 20 epileptic children treated in monotherapy with valproic acid (VPA) for 6-52 months and in 2 matched control groups. The frequencies of SCE in the VPA-treated epileptic children were significantly higher than in the 2 control groups (p less than 0.01); rates of chromosome aberrations were slightly higher but not significantly different from the 2 control groups. We also examined SCE in 10 epileptic children before and after they took sodium valproate for 6-7 months; there was a statistically significant change in SCE following VPA. 9 normal children whose lymphocytes were exposed in vitro to sodium valproate (5-20 micrograms/ml) showed a significant increase in SCE.     

丝裂霉素C诱发中国仓鼠体外培养细胞姐妹染色单体互换的研究

本文对不同年龄中国仓鼠各种组织的体外培养细胞姐妹染色单体互换(SCE)频率进行了比较研究。实验结果表明,体外培养细胞的自发SCE频率与动物年龄无关,相同组织细胞经MMC处理后,老龄仓鼠SCE频率比幼龄仓鼠SCE频率明显低。心脏和皮肤细胸的SCE频率高于肺和尾的SCE频率。     

Cytogenetic analysis in workers occupationally exposed to nickel carbonyl

Chromosomal aberration and sister-chromatid exchange (SCE) base-line frequencies and SCE frequencies induced by 10 ng/ml mitomycin C (MMC) were analysed in cultured peripheral lymphocytes of 65 workers occupationally exposed to nickel carbonyl Ni(CO)4. The subjects were divided into 4 groups: (1) control; (2) exposed to nickel carbonyl (= exposed); (3) cigarette smokers; (4) smoking-exposed. The results show that there are no significant differences in chromosomal aberration frequencies, breaks or gaps, between the various groups. However, the SCE base-line frequency of the smoking-exposed group, with an average of 7.7/cell, was significantly higher than that of the control group, with an average of 6.5/cell (P less than 0.01), and also than that of the exposed group with an average of 5.9/cell (P less than 0.01). Similarly, the SCE frequency induced by 10 ng/ml MMC in the smoking-exposed group which averaged 15.5/cell was significantly higher than that of the control group (average of 13.2/cell (P less than 0.05], and also than that of the exposed group with an average of 12.3/cell (P less than 0.01). Under our experimental conditions, it may be that the level of exposure was not high enough to elicit an increase in chromosomal aberrations and SCE frequencies in the non-smoker exposed group. The fact that an increase in SCE frequencies was only found in the smoking-exposed group implies that the two factors, smoking and exposure to nickel carbonyl, are jointly responsible for the result.     

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.     

Bimodal distribution of sensitivity to SCE induction by diepoxybutane in human lymphocytes. II. Relationship to baseline SCE frequency

Environmental and genetic factors have been implicated as important sources of individual variation in baseline sister-chromatid exchange (SCE) frequency in humans. The current study was designed to test whether the frequency of baseline SCEs in 58 normal blood donors is associated with previously observed variations in SCE frequencies induced by diepoxybutane (DEB). Because 12 subjects were current cigarette smokers and smoking is known to be an in vivo inducer of baseline SCE frequencies, we specifically tested whether higher baseline SCE frequencies in smokers would be associated with in vitro sensitivity to SCE induction by DEB. Analysis of variance showed that DEB-induced SCE frequencies were significantly associated with baseline SCE frequencies; those who were sensitive to SCE induction by DEB were more likely to have higher baseline SCE frequencies. This effect, however, was independent of in vivo induction of SCE by smoking. Chromosomal sensitivity to the induction of SCE by DEB explained approx. 15-20% of the variation in baseline SCE. This was similar in magnitude to the effect of cigarette smoking. Because increased sensitivity to DEB-induced SCEs is common in normal blood donors (approx. 24%) and is associated with an increase in baseline SCEs, it should be investigated as a source of bias and/or a potential marker of sensitivity to environmental mutagens in future cytogenetic studies.     

The genotoxic risk of underground coal miners from Turkey

A cytogenetic monitoring study was carried out on a group of workers from a bituminous coal mine in Zonguldak province of Turkey, to investigate the genotoxic risk of occupational exposure to coal mine dust. Cytogenetic analysis, namely sister chromatid exchanges (SCEs), chromosomal aberrations (CAs) and micronucleus (MN) tests were performed on a strictly selected group of 39 workers and compared to 34 controls matched for gender, age, and habit. Smoking and age were considered as modulating factors. Both SCE and CA frequencies in coal miners appeared significantly higher than in controls. Similarly, there was a significant increase in the frequency of total micronuclei in exposed group as compared to control group. The effect of smoking on the level of SCE and MN was significant in the control group. A positive correlation between the age and the level of SCE was also found in controls. The frequencies of both SCE and CA were significantly enhanced with the years of exposure. The results of this study demonstrated that occupational exposure to coal mine dust leads to a significant induction of cytogenetic damage in peripheral lymphocytes of workers engaged in underground coal mining.     

Chromosomal Aberrations (CA), Sister Chromatid Exchanges (SCE), and High-Frequency Cells (HFC) Frequencies in Peripheral Blood Lymphocytes of Tunisian Gasoline Truck Loaders

Gasoline constitutes a mixture of chemicals that contain well-known genotoxicants. Thus, chronic occupational exposure to gasoline may be considered to possess genotoxic risk. In this study, the frequencies of total chromosomal aberrations (TCA), aberrant cells (Ab.c.), sister chromatid exchanges (SCE), high-frequency cells (HFC), and high-frequency cell individual (HFI) were investigated in peripheral blood lymphocytes from 17 gasoline-exposed workers (10 smokers and 7 non-smokers) and 22 unexposed reference subjects (12 smokers and 10 non-smokers). The exposed subjects were gasoline truck loaders at a gasoline company from Tunis City, north of Tunisia. The results indicate multiple CA, such as dicentrics (DIC), chromatid breaks (SB), and chromosome breaks (DB). A significant difference was observed in TCA and Ab.c. frequencies between exposed and unexposed groups (p < 0.01). A significant difference was found in frequencies of SCE (p < 0.01) and HFI (p < 0.05) between exposed and unexposed groups. SCE and TCA frequencies of smokers were found to be significantly higher than those of non-smokers in both groups. There was an interaction between gasoline exposure and smoking habit for TCA (p = 0.020), but not for SCE. Our findings indicate that gasoline truck loaders were under risk of significant cytogenetic damage that was enhanced by their smoking habit.     

The genotoxic risk of underground coal miners from Turkey

A cytogenetic monitoring study was carried out on a group of workers from a bituminous coal mine in Zonguldak province of Turkey, to investigate the genotoxic risk of occupational exposure to coal mine dust. Cytogenetic analysis, namely sister chromatid exchanges (SCEs), chromosomal aberrations (CAs) and micronucleus (MN) tests were performed on a strictly selected group of 39 workers and compared to 34 controls matched for gender, age, and habit. Smoking and age were considered as modulating factors. Both SCE and CA frequencies in coal miners appeared significantly higher than in controls. Similarly, there was a significant increase in the frequency of total micronuclei in exposed group as compared to control group. The effect of smoking on the level of SCE and MN was significant in the control group. A positive correlation between the age and the level of SCE was also found in controls. The frequencies of both SCE and CA were significantly enhanced with the years of exposure. The results of this study demonstrated that occupational exposure to coal mine dust leads to a significant induction of cytogenetic damage in peripheral lymphocytes of workers engaged in underground coal mining.     

Sister-chromatid exchange frequencies in lymphocytes of controls and patients with connective tissue diseases

It has been considered by some workers that sister-chromatid exchange (SCE) frequencies are elevated in patients with scleroderma and systemic lupus erythematosus (SLE). However, these observations were based on limited numbers of patients. Other have postulated the presence of a defect in DNA repair in cells from patients with various connective tissue diseases, including scleroderma and SLE. We report our findings from a large survey of SCE frequencies in patients with connective tissue diseases. Their diagnoses are scleroderma, SLE, rheumatoid arthritis, juvenile chronic arthritis, Behcet's syndrome and polyarteritis nodosa. These patients had never received cytotoxic drugs. Healthy individuals, hospital patients with diagnoses other than connective tissue disease and relatives of patients with scleroderma have been used as controls. The results have been analysed by generalized linear modelling, and we have shown that patients with SLE and Behcet's syndrome and controls with viral infections have elevated SCE frequencies, both before and after adjustments have been made for the effect on SCEs of an individual's age, smoking habits, sex and race. The SCEs of patients with scleroderma and their relatives were normal. SCE frequencies increased with age by 4% per decade and the SCE frequencies of smokers were approximately 12% higher than those of nonsmokers of similar age. The sex of an individual did not significantly affect SCEs but individuals from the Middle East were found to have lower counts than those originating from other parts of the world.     

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 less than 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 micrograms/ml), hycanthone (0.1 micrograms/ml) and gamma-radiation (0.1 Gy) revealed a significant (P less than 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 exchanges and high-frequency cells in men environmentally and occupationally exposed to ambient air pollutants: an intergroup comparison with respect to seasonal changes and smoking habit

Sister chromatid exchanges (SCE) and high-frequency cells (HFC) were measured in peripheral blood lymphocytes from men environmentally and occupationally exposed to a mixture of ambient air pollutants. The environmentally exposed individuals were inhabitants of the industrial region of Upper Silesia; those occupationally exposed were Silesian cokery or steel plant workers, while the control group consisted of rural region residents. A total of 147 males were enrolled in the study. Blood samples were collected in winter (February) and summer (September) seasons. Three major areas were investigated during the study: exposure-based dose dependency, seasonal changes, and influence of smoking habits on the SCE frequencies. The latter is frequently reported as a confounding factor in SCE analyses. In both winter and summer samples, statistically significant increases of SCE were observed in the environmentally and occupationally exposed groups compared to the controls (p<0.001). The difference between both exposed groups was also significant (p<0.001). An intergroup comparison was based on ANOVA after adjustment for smoking status. In all three groups of interest, a seasonal variation was found with higher levels in winter. However, in a part of the study in which each donor served as his own control, statistical differences were only found within the exposed groups. Control region inhabitants did not have significantly higher frequencies of SCE in winter, compared to summer samples. The impact of two major confounders, age of the donor and smoking habit, was investigated by multiple regression analysis. Smoking was a major factor influencing the level of SCE. Nevertheless, the effect was seen in winter samples only, which suggests an additive response and adds new information to this known effect.