Variation in the human lymphocyte sister-chromatid exchange frequency: results of a long-term longitudinal study

The variation in lymphocyte sister-chromatid exchange (SCE) frequency as a function of time was investigated in nonsmokers and smokers. The smokers were divided into 3 groups depending on their smoking status. The group termed 'smokers' participated in a program to stop smoking but did not reduce or eliminate their use of tobacco; 'smoke enders' successfully completed the smokending program and remained free of tobacco for the duration of the study, while the 'variable' group stopped smoking for a limited time but then resumed smoking. 8 or more blood samples per person were obtained over a period of at least 12 months. The SCE frequencies for each of these groups were compared with each other and with those of two previous longitudinal study groups from our laboratory. The proportion of high-frequency cells (HFCs) was also determined for each sample. The results confirm our previous finding that SCE frequencies and the proportion of HFCs observed in separate samples from the same individual are more likely to be different as the time between samples increases. We also show that smokers have significantly more SCEs and HFCs than do nonsmokers, that SCE frequencies in smokers do not decline for at least 12 months when smoking is stopped, and that among smokers, significant seasonal variation in the SCE frequency occurs. These results provide useful information concerning the effects of smoking upon SCE frequencies, and will be helpful in designing and interpreting the results of long-term human population cytogenetic studies.     

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.     

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.     

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.     

Bimodal distribution of sensitivity to SCE induction by diepoxybutane in human lymphocytes. I. Correlation with chromosomal aberrations

We carried out a cross-sectional analysis of sister-chromatid exchanges (SCEs) and chromosomal aberrations induced by diepoxybutane (DEB) in lymphocyte cultures from 58 normal blood donors. DEB-induced SCE frequencies were measured in all subjects and chromosomal aberrations in 18. Analysis of variance was used to assess the contributions of exposure to organic solvents, age, smoking history, alcohol and coffee consumption, and red and white blood cell counts to variations in DEB-induced SCEs. In 10 individuals, the epoxide-detoxifying enzyme, glutathione (GSH)-S-transferase mu, was also measured. We observed a bimodal distribution of DEB-induced SCEs in the study population. Approx. 24% of the individuals were twice as sensitive to the induction of SCEs by DEB as the remaining 76%. Lymphocytes from persons sensitive to SCE induction by DEB contained a 4.4-fold increase in the number of DEB-induced chromatid deletions and exchanges. Within sensitive and resistant groups, significant interindividual variations in DEB-induced SCE frequencies were noted. Cigarette smoking was weakly associated with lower SCE frequencies within each group. Genetic deficiency in GSH-S-transferase mu was not correlated with increased sensitivity to SCE induction by DEB. Sensitivity to induction of SCEs by DEB can be rapidly determined and may be a marker of sensitivity to the induction of genotoxicity by certain classes of mutagens.     

Cytogenetic monitoring of a group of Italian floriculturists: no evidence of DNA damage related to pesticide exposure

The induction of sister chromatid exchanges (SCE), structural chromosome aberrations (CA) or micronuclei (MN) was investigated in peripheral lymphocytes of a group of Italian floriculturists exposed to a mixture of pesticides. No statistically significant difference in the frequencies of cytogenetic damage was detected between exposed and control subjects. Assessment of the effect of confounding factors indicated that smoking affected both SCE and CA frequencies. Multiple regression analysis showed that in heavy smokers (≥ 20 cigarettes/day), SCE and CA levels increased significantly by 17% and 54%, respectively, as compared to non-smokers.     

Analysis of sister chromatid exchanges in lymphocytes cultured from 71 healthy men

Sister chromatid exchanges (SCE) were analyzed in peripheral blood lymphocytes from a select group of 71 healthy men, 56 nonsmokers and 15 cigarette smokers. In addition to estimating baseline SCE, data were examined to seek relationships of SCE frequencies to age and smoking. The baseline value of 7.53 SCE per cell from the 56 nonsmokers was within the range (5.60 to 9.10 SCE/cell) reported for other human populations. No relationship was found between the mean SCE frequency per cell and age. However, a significant increase in the SCE mean value was observed in smokers as compared to nonsmokers. The results of this study are compared with those of other reports on SCE effects of age and smoking.Abbreviations BUdR 5-bromo,2-deoxyuridine - SCE sister chromatid exchange     

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.     

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.     

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.     

Sister chromatid exchange rate from pleural fluid cells in patients with malignant mesothelioma

This study assessed the impact of malignant mesothelioma on the frequencies of sister chromatid exchange (SCE) in the pleural effusion cells. Ten patients with mesothelioma and 20 control subjects were included in the study. The control subjects were the patients with tuberculosis pleurisy, and the remaining 10 subjects of control group were healthy volunteers and only heparinized blood samples were collected from these subjects. The pleural effusion cells were cultured with conventional culture methods. The samples were obtained from the patients after histopathologic confirmation of the malignancy but before the initiation of chemotherapy or radiotherapy. At the end of the culture period and 48 h prior the harvesting, BrdU was added into flasks. Totally, 100 metaphases were scored for each sample. In this study, we found that the SCE frequencies of malignant pleural mesotheliomas were significantly higher than the control subjects (P<0.001). Six of 10 patients came from central Anatolia, which is of great importance due to high rate of exposure to asbestosis in this region.     

Prospective study of factors predicting outcome of transdermal nicotine treatment in smoking cessation.

OBJECTIVE--To assess the factors associated with cessation of smoking with transdermal nicotine and brief behavioural counselling. DESIGN--Interviews, treatment, and follow up for 26 weeks. SUBJECTS--1481 subjects recruited by mass media publicity who smoked > or = 15 cigarettes a day and were motivated to stop smoking. INTERVENTIONS--Twelve weeks'' treatment with transdermal nicotine and brief behavioural counselling at monthly visits. MAIN OUTCOME MEASURE--Sustained smoking cessation for the 28 days before the visit at week 26 verified by expired carbon monoxide concentrations. The logistic regression analysis included all subjects. RESULTS--Most subjects were dependent on nicotine, and the mean (SD) number of cigarettes smoked a day was 32 (12). Overall, 316/1481 subjects (21.3%) stopped smoking. Factors associated with stopping were being male (adjusted odds ratio 2.0; 95% confidence interval 1.5 to 2.7), age > or = 40 years (1.5; 1.1 to 2.0), living with a spouse or partner (1.5; 1.1 to 2.1), motivation ("want to quit" 1.7; 1.2 to 2.3), and concern about weight gain (1.7; 1.3 to 2.2). Negative associations were smoking marijuana (0.4; 0.2 to 0.8) and the presence of other smokers in the household (0.8; 0.6 to 0.9). Almost all subjects who smoked three or more cigarettes in the first four weeks of treatment resumed smoking in the long term (525/547, 96%). CONCLUSIONS--Age, sex, marital status (living with a spouse or partner), motivation, concern about weight gain, recent marijuana smoking, and other smokers in the household were baseline factors associated with differences in outcome of smoking cessation attempts. Smoking three or more cigarettes in the first few weeks after stopping strongly predicted long term relapse.     

Differences in pharmacokinetic and electroencephalographic responses to caffeine in sleep-sensitive and non-sensitive subjects

The present study investigated pharmacokinetic and electroencephalographic responses to caffeine (140 mg) in two groups of healthy volunteers reporting, or not, caffeine-related sleep disturbances. Significant differences in caffeine consumption and smoking habits were observed between the two groups. Plasma samples were taken from each subject before (T0) and after caffeine intake at 0.5, 1, 2, 4, 6 and 24 h. Three pharmacokinetic parameters: half-life (t1/2), maximum time (Tmax) and maximum plasma concentration (Cmax) were calculated from caffeine plasma concentration measurements determined by reversed phase HPLC analysis. Caffeine-sensitive subjects showed significantly greater half-life values when calculated on 24 h after the administration than tolerant subjects (p<0.05). Since the elimination kinetics were similar on the first 6 h after caffeine administration, the increased caffeine clearance observed overnight, when smoking was resumed in the control group, may indicate a short delay for the induction of hepatic cytochrome, reported here for the first time. Electrophysiological responses to caffeine, including vigilance and cortical activity, were assessed by ambulatory electroencephalographic (EEG) recorded during a period of 6 h before and after caffeine consumption. Following caffeine intake, the caffeine-intolerant subjects presented an increase in vigilance levels with faster peak alpha, beta frequency and lower delta and theta power when compared to tolerant subjects. Pharmacokinetic parameters and EEG data showed significant differences between sleep-sensitive and control subjects. These variations may be, in part, explained by cigarette smoking and the higher caffeine intake observed in the subjects of the control groups while caffeine sleep-sensitive subjects have a significantly lower caffeine intake, as already reported in previous studies on patients with sleep disturbances.     

Circadian and Ultradian Rhythms in Heart Rate and Motor Activity of Smokers,Abstinent Smokers,and Nonsmokers

In a field study, heart rate and motor activity were assessed continuously in 12 male smokers during 2 smoking and 2 abstinence days and in 12 male nonsmokers during 4 days. A circadian analysis revealed earlier activity acrophases in smokers than nonsmokers and earlier heart rate acrophases in abstinent than smoking smokers. Furthermore, heart rate acrophases of smoking smokers significantly anticipated activity acrophases;, whereas in abstinent smokers and nonsmokers the two parameters oscillated in phase. With the use, in smoking smokers, of the individual average smoking interval as a hypothetical ultradian period length, significant periodicities were found for heart rates in 16 and for activity in 15 of 24 observation days. These rhythms were nicotine independent and based on heart rate and activity increases prior to lighting up the cigarettes. Individual frequency spectra for the 16 h after getting up and the 7 h after going to bed did not reveal single dominant frequencies but rather complex frequency distributions. Power spectra of the daytime data revealed no group differences for activity and no heart rate differences between smoking smokers and nonsmokers. In abstinent smokers, however, a significant reduction of heart rate frequencies slower than 1 cycle/135 min and a significant increase of heart rate frequencies faster than 1 cycle/20 min were observed as compared with all other groups. This effect persisted over the 2 abstinence days, suggesting an activity-independent change in the frequency distribution of heart rates after quitting smoking.     

Circadian and Ultradian Rhythms in Heart Rate and Motor Activity of Smokers, Abstinent Smokers, and Nonsmokers

In a field study, heart rate and motor activity were assessed continuously in 12 male smokers during 2 smoking and 2 abstinence days and in 12 male nonsmokers during 4 days. A circadian analysis revealed earlier activity acrophases in smokers than nonsmokers and earlier heart rate acrophases in abstinent than smoking smokers. Furthermore, heart rate acrophases of smoking smokers significantly anticipated activity acrophases;, whereas in abstinent smokers and nonsmokers the two parameters oscillated in phase. With the use, in smoking smokers, of the individual average smoking interval as a hypothetical ultradian period length, significant periodicities were found for heart rates in 16 and for activity in 15 of 24 observation days. These rhythms were nicotine independent and based on heart rate and activity increases prior to lighting up the cigarettes. Individual frequency spectra for the 16 h after getting up and the 7 h after going to bed did not reveal single dominant frequencies but rather complex frequency distributions. Power spectra of the daytime data revealed no group differences for activity and no heart rate differences between smoking smokers and nonsmokers. In abstinent smokers, however, a significant reduction of heart rate frequencies slower than 1 cycle/135 min and a significant increase of heart rate frequencies faster than 1 cycle/20 min were observed as compared with all other groups. This effect persisted over the 2 abstinence days, suggesting an activity-independent change in the frequency distribution of heart rates after quitting smoking.     

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 frequencies in postmenopausal hormone replacement patients

Our objective was to evaluate the frequency of sister-chromatid exchange (SCE) during hormone replacement therapy in postmenopausal women. Thirty-four asymptomatic postmenopausal women with a minimum 12 months since last menstrual period and surgical menopausal women were included in the study. Seventeen patients who were in spontaneous menopause were administered conjugated estrogen and medroxyprogesterone acetate (group A), and the others who were in surgical menopause were given 17beta-estradiol only (group B). Peripheral lymphocytes were obtained at the beginning and at the end of the third month of therapy. The mean age of the patients was 50. 67+/-4.79. There were statistically significant differences in terms of SCE frequencies between pre- and posttreatment levels of both groups (p<0.001 and p=0.003, respectively). It is likely that estrogens with or without progesterone have an effect in increased SCE frequency and this issue may be an evidence for the increased potential for malignancies.     

SCE frequencies in rabbit lymphocytes as a function of time after an acute dose of cyclophosphamide

Following acute and chronic exposures to various chemicals in vivo, the average SCE frequency in human and rabbit lymphocytes has generally been shown to decrease with time posttreatment. The rate of this decline varies, however, and little data have been published pertaining to the decrease in SCEs soon exposure. To gain more information about the immediate decline in SCEs with time, we injected rabbits with a single dose of 35 mg/kg cyclophosphamide (CP) and determined SCE levels in circulating lymphocytes at various times 5 h to 2 weeks after treatment. We observed a rapid decline in SCE frequencies within 5 days, and by 10 days post-exposure the SCE levels were back to control values. The distributions of SCEs among cells and the number of circulating lymphocytes were also analyzed at each time. Within 2–3 days posttreatment we observed a rapid loss of cells with high SCE levels concomitantly with a rapid decline in circulating lymphocytes and a decrease in the average SCE frequency. When the number of lymphocytes began to increase, the number of cells with normal SCE values also increased. By 10–11 days after CP, the lymphocyte count had recovered, the SCE frequency had returned to control levels, and the distribution of SCEs among cells was almost identical to the control distribution. These data, in addition to published information on rabbit lymphocyte lifespan, suggest that the decline in SCE levels with time posttreatment is a function of lymphocyte turnover.     

Evolution of sister-chromatid exchanges (SCE) in rat bone marrow cells as a function of time after 2 Gy of whole-body neutron irradiation

We scored sister-chromatid exchanges (SCE) in bone marrow cells in 3-month-old rats as a function of time after 2 Gy of whole-body neutron irradiation. This dose reduced the mean survival time to 445 days after irradiation, and induced more than one tumor per animal; by 200 days post irradiation, all animals bore tumors at autopsy, but bone marrow was not a significant target for tumor induction. In controls, the mean SCE/cell remained constant from 3 to 24 months of age (2.38 SCE/cell, S.D. = 0.21). Irradiation induced 2 distinct increases in SCE: the first occurred during the days following exposure, and the second, from days 150 to 240. Thereafter, SCE values formed a plateau at 3.37 SCE/cell (S.D. = 0.39) until day 650. Between the two increases (i.e. from days 15 to 150), SCE dropped to control values. Analysis of SCE distribution per cell shows that the entire dividing cell population altered homogeneously during the increase in SCE. These results suggest that in our irradiated rats, the second increase in SCE coincides with tumor growth, whereas the first increase might be due to DNA damage that was rapidly repaired.     

Sister chromatid exchanges in human leukocyte chromosomes: Spontaneous and induced frequencies in early- and late-proliferating cells in vitro

Summary Human leukocyte cultures were pulse-treated with the trifunctional alkylating mutagen trenimon in a final concentration of 10^-7 M for 15–20 h after culture start, i.e., in the G₁ phase of the cell cycle. At 24 h after culture start bromodeoxyuridine (BUdR) was added to the trenimon-treated cultures and to several untreated cultures running in parallel. The series treated with BUdR only and the series treated with BUdR+trenimon were each used to prepare two cultures at different culture times. Mitoses were collected during consecutive intervals of 12 h from 30 h up to 102 h after culture initiation by colcemid. For all preparation times (42 h, 54 h, 66 h, 78 h, 90 h, and 102 h) the frequencies of first, second, and third and further mitoses were determined in the BUdR- and in the BUdR+trenimon-treated series. In the trenimon-treated series a clear cell cycle delay was detected as compared with the normal distribution of different types of mitoses found in series treated with BUdR only. Spontaneous and trenimon-induced sister chromatid exchange (SCE) frequencies were determined in second mitoses occurring at 66 h, 78 h, 90 h, and 102 h after culture start. For all these preparation times about six SCE per metaphase were consistently found in BUdR-treated, and about 19 SCE per metaphase in BUdR+trenimon-treated series, indicating a homogeneous sensitivity of early- and late-proliferating cells with respect to the induction of SCE.This paper is dedicated to Prof. B. Erich Wolf on the occasion of his 70th birthday