Patients with rheumatoid arthritis have better functional and working ability but poorer general health and higher comorbidity rates today than in the late 1990s.

OBJECTIVES: Better treatment strategies and therapeutic options have changed the treatment of rheumatoid arthritis (RA) during the past decade. Our objective was to examine clinical and patient-reported outcomes in patients with RA treated in 1998-99 and 2011-12. METHOD: The cross-sectional observational study included 303 consecutive outpatients (n = 103 in 1998-99 and n = 200 in 2011-12) from the same outpatient clinic. Patient questionnaires included patients' sociodemographics, the Health Assessment Questionnaire (HAQ) for functional ability, the Nottingham Health Profile (NHP) for health-related quality of life (HRQoL), self-reported general health (GH), and operations performed due to RA. A clinical examination was conducted for all patients. Comorbidities according to the Charlson Comorbidity Index (CCI), anti-rheumatic drugs and medications were recorded and the HAQ and NHP dimensions calculated. The results from these two patient cohorts were compared. RESULTS: The cohorts were comparable with regard to age, sex, and RA duration while the patients in the 2011-12 cohort were less often seropositive for rheumatoid factor (RF), had a better socioeconomic situation, better functional and working ability, and a decreased rate of RA surgery. The patients in 2011-12 had higher comorbidities and poorer GH while the HRQoL dimensions did not differ between the cohorts except for better mobility in 2011-12. Methotrexate (MTX) and combinations of conventional anti-rheumatic drugs were more frequently used in 2011-12. Biologicals were used only in 2011-12. CONCLUSIONS: According to our results, more active anti-rheumatic therapy coincides with better RA-related outcomes. However, the result was the opposite with regard to overall health and comorbidities. Is this a new challenge in the treatment RA?

Waist circumference based abdominal obesity may be helpful as a marker for unmet needs in patients with RA.

OBJECTIVES: To assess the impact of abdominal obesity (AO) on disease severity, cardiovascular risk factors, and patient-reported outcomes (PROs) in patients with rheumatoid arthritis (RA). METHOD: Two hundred and thirty consecutive outpatients were cross-sectionally assessed. Waist circumference (WC) with a cut-off point of ≥ 102 cm in men and ≥ 88 cm in women indicated AO. Clinical assessment included joint counts, radiographs of small joints, and laboratory tests. Comorbidities and medication were verified from the patients' database. Patient questionnaires included sociodemographics, pain intensity, global disease activity, the Beck Depression Inventory (BDI), the Health Assessment Questionnaire (HAQ), physical activity level, and the 36-item Short Form Health Survey (SF-36). Metabolic syndrome (MetS) was defined according to the criteria of National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III). The association of AO with the 28-joint count Disease Activity Score (DAS28) and mental (MCS) and physical component scores (PCS) of the SF-36 and the HAQ was assessed by using regression models with the propensity score as a covariate. RESULTS: The AO prevalence was 52% in the 200 eligible patients. In a univariate analysis, AO was associated with cardiovascular risk factors, low HAQ score, physical inactivity, disease activity parameters, impaired MCS, higher pain, and increased use of biological drugs and antidepressants. In a multivariable model, only poorer DAS28 (p = 0.018) and poorer HAQ score (p = 0.004) remained significantly associated with AO. CONCLUSIONS: AO is highly prevalent in patients with RA. In addition to cardiovascular risk factors, AO is associated with higher disease activity, higher disability, physical inactivity, more patients' perception of pain, and poorer mental health. Multifaceted promotion of lifestyle habits would be beneficial for improving AO-related health outcomes in patients with RA.

A nationwide cross-sectional overview of patients with rheumatoid arthritis followed in outpatient specialty clinics in Finland.

OBJECTIVES: We aimed to conduct a cross-sectional overview of patients with rheumatoid arthritis (RA) in outpatient specialized clinics in Finland. METHOD: Consecutive patients were enrolled in the study. The data collected comprised demographic, disease- and treatment-related variables. RESULTS: Between November 2011 and May 2012, 890 patients with RA (77% female) were enrolled from 14 sites. The median age was 59.8 years and the time from diagnosis 7.2 years. Values for the Disease Activity Score using 28 joint counts (DAS28) ranged from 0.28 to 6.61 (median 2.55) with 52% and 70% of patients reaching remission and low disease activity, respectively. Rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies were evident in 70% and 63% of patients, respectively. Median Health Assessment Questionnaire (HAQ) scores with and without aids and devices were 0.75 [interquartile range (IQR) 0.13-1.38] and 0.63 (IQR 0.13-1.13), respectively. Conventional disease-modifying anti-rheumatic drugs (DMARDs) were used by 91% of patients. A triple therapy of methotrexate (MTX), hydroxychloroquine (HCQ), and sulfasalazine (SSZ) was used by 15%, other MTX-based combination by 30%, MTX alone by 20%, and other DMARDs alone or in combination by 26% of patients. In addition, glucocorticoids and biologics were taken by 58% and 21% of patients, respectively. Of the 184 biologics users, 18% were not using DMARDs concomitantly. CONCLUSIONS: Our cross-sectional review of patients with RA revealed that > 50% of patients were in remission according to DAS28. Comparison with previous studies revealed a reduction in disease activity of prevalent RA cases, possibly resulting from increased use of aggressive anti-rheumatic treatments.

Thyroid nodularity and cancer among Chernobyl cleanup workers from Estonia.

Thyroid examinations, including palpation, ultrasound and, selectively, fine-needle aspiration biopsy, were conducted on nearly 2,000 Chernobyl cleanup workers from Estonia to evaluate the occurrence of thyroid cancer and nodular thyroid disease among men with protracted exposure to ionizing radiation. The examinations were conducted in four cities in Estonia during March-April 1995, 9 years after the reactor accident. The study population was selected from a predefined cohort of 4,833 cleanup workers from Estonia under surveillance for cancer incidence. These men had been sent to Chernobyl between 1986 and 1991 to entomb the damaged reactor, remove radioactive debris and perform related cleanup activities. A total of 2,997 men were invited for thyroid screening and 1,984 (66%) were examined. Estimates of radiation dose from external sources were obtained from military or other institutional records, and details about service dates and types of work performed while at Chernobyl were obtained from a self-administered questionnaire. Blood samples were collected for assay of chromosomal translocations in circulating lymphocytes and loss of expression of the glycophorin A (GPA) gene in erythrocytes. The primary outcome measure was the presence or absence of thyroid nodules as determined by the ultrasound examination. Of the screened workers, 1,247 (63%) were sent to Chernobyl in 1986, including 603 (30%) sent in April or May, soon after the accident. Workers served at Chernobyl for an average of 3 months. The average age was 32 years at the time of arrival at Chernobyl and 40 years at the time of thyroid examination. The mean documented radiation dose from external sources was 10.8 cGy. Biological indicators of exposure showed low correlations with documented dose, but did not indicate that the mean dose for the population was higher than the average documented dose. Ultrasound examinations revealed thyroid nodules in 201 individuals (10.2%). The prevalence of nodules increased with age at examination, but no significant associations were observed with recorded dose, date of first duty at Chernobyl, duration of service at Chernobyl, building the sarcophagus or working on the roof of neighboring buildings or close to the damaged reactor. Nodularity showed a nonsignificant (p(1) = 0.10) positive association with the proportion of lymphocytes with chromosome translocations, but associations with the frequency of variant erythrocytes in the GPA assay were weak and unstable (p(1) > or = 0.46). The majority of fine-needle biopsies taken on 77 study participants indicated benign nodular disease. However, two cases of papillary carcinoma and three benign follicular neoplasms were identified and referred for treatment. Both men with thyroid cancer had been sent to Chernobyl in May of 1986, when the potential for exposure to radioactive iodines was greatest. Chernobyl cleanup workers from Estonia did not experience a markedly increased risk of nodular thyroid disease associated with exposure to external radiation. Possible reasons for the apparent absence of effect include low radiation doses, the protracted nature of the exposure, errors in dose measurement, low sensitivity of the adult thyroid gland or the insufficient passage of time for a radiation effect to be expressed.

Do recorded doses overestimate true doses received by Chernobyl cleanup workers? Results of cytogenetic analyses of Estonian workers by fluorescence in situ hybridization.

Studies of workers who were sent to Chernobyl after the 1986 reactor accident are being conducted to provide a better understanding of the effects of chronic low-dose radiation exposures. A crucial component to these investigations is an accurate assessment of the radiation doses received during the cleanup activities. To provide information on biological measurements of dose, fluorescence in situ hybridization (FISH) with whole-chromosome painting probes has been applied to quantify stable chromosome aberrations (translocations and insertions) among a defined cohort of 4,833 cleanup workers from Estonia. Cytogenetic analysis of 48-h lymphocyte cultures from 118 Estonian cleanup workers (10.3 cGy mean recorded dose; 25 cGy maximum), 29 Estonian population controls and 21 American controls was conducted by three laboratories. More than 258,000 painted metaphases were evaluated. Overall, we observed lower translocation frequencies than has been reported in previous studies using FISH among Chernobyl cleanup workers. In our data, a clear association with increased levels of translocations was seen with increasing age at blood drawing. There was no correlation, however, between aberration frequency and recorded measurements of physical dose or any category of potential high-dose and high-dose-rate exposure such as being sent to Chernobyl in 1986, working on the roof near the damaged nuclear reactor, working in special zones or having multiple tours. In fact, the translocation frequency was lower among the exposed workers than the controls, though not significantly so. To estimate the level of effect that would have been expected in a population of men having an average dose of approximately 10 cGy, blood from six donors was exposed to low-LET radiation, and more than 32,000 metaphases were scored to estimate dose-response coefficients for radiation-induced translocations in chromosome pairs 1, 2 and 4. Based on these results, we estimate that had this group of 118 men received an average whole-body dose of 10-11 cGy, as chronic or acute exposures, an increase in the mean frequency of chromosome translocations of more than 40-65% would have been observed in their lymphocytes compared to findings in nonirradiated controls. In spite of evaluating more than a quarter of a million metaphases, we were unable to detect any increase in the mean, median or range in chromosome aberrations in lymphocyte cultures from a group of Estonian men who took part in the cleanup of the Chernobyl nuclear power site and those who did not. We conclude that it is likely that recorded doses for these cleanup workers overestimate their average bone marrow doses, perhaps substantially. These results are consistent with several negative studies of cancer incidence in Chernobyl cleanup workers and, if borne out, suggest that future studies may not be sufficiently powerful to detect increases in leukemia or cancer, much less distinguish differences between the effects of chronic compared to brief radiation exposures.

In situ hybridization of ovalbumin mRNA in the chick oviduct reveals target cell specificity for estrogen and progesterone.

An in situ hybridization method using paraffin-embedded sections was used to characterize the chicken oviduct cells synthesizing ovalbumin mRNA due to the action of estrogen and progesterone. The cytodifferentiation of the oviduct cells was induced by 17 beta-estradiol administration to newly hatched female chicks. To avoid possible effect of estrogen on the action of progesterone the chicks were withdrawn from the estrogen by six days withdrawal period without hormone treatment. Ovalbumin mRNA was not synthesized after a period of estrogen withdrawal. Administration of estrogen induced ovalbumin mRNA in the tubular gland cells. Administration of progesterone induced the expression of ovalbumin mRNA in the surface epithelial cells. It was also found that progesterone induced mucus producing goblet cells in the surface epithelium. Estrogen did not have an effect on the mucus production, which suggests that progesterone could induce the terminal differentiation of the goblet cells. We conclude that the expression of ovalbumin in the surface epithelial cells and in the tubular gland cells is specific for progesterone and estrogen, respectively.

Inducibility of the avidin gene by progesterone is suppressed during estrogen-induced cytodifferentiation.

We have studied epithelial differentiation of the chick oviduct as induced by diethylstilbestrol (DES) and 17 beta-estradiol (E2). The proportion of goblet cells in the oviduct was slightly higher after E2 than after DES treatment. Also avidin induction by progesterone was stronger following DES than E2 priming. In the estrogen pretreated oviduct epithelium, avidin expression was induced by progesterone in the surface epithelial cells, protodifferentiated gland cells and tubular gland cells, but not in goblet cells. During prolonged estrogen treatment, however, the inducibility of avidin by progesterone ceased in tubular gland cells but not in surface epithelial cells. The estrogen action on the expression of avidin could be explained by estrogen-induced terminal differentiation of the epithelial gland cells or by a direct effect of estrogen on the progesterone action, for instance interaction of estrogen receptor and progesterone receptor in the regulation of transcription.

Methods for improving the yield and quality of metaphase preparations for FISH probing of human lymphocyte chromosomes.

Procedures are described for the in vitro culture of human lymphocytes, which have been concentrated by density gradient centrifugation, and for a modified slide-making technique for the fixed cells. The method yields improved percentages of mitotic cells which are largely synchronized at harvest. Controlled placement of fixed cells on slides produces well-spread metaphase preparations with little background material to interfere with fluorescence in situ hybridization (FISH) probe procedures. The FISH reagents and microscope scanning time required are minimized by concentrating cells in a defined area of the slide.

Cancer predictive value of cytogenetic markers used in occupational health surveillance programs.

It has not previously been clear whether cytogenetic biomarkers in healthy subjects will predict cancer. Earlier analyses of a Nordic and an Italian cohort indicated predictivity for chromosomal aberrations (CAS) but not for sister chromatid exchanges (SCES). A pooled analysis of the updated cohorts, forming a joint study base of 5271 subjects, will now be performed, allowing a more solid evaluation. The importance of potential effect modifiers, such as gender, age at testing, and time since testing, will be evaluated using Poisson regression models. Two other potential effect modifiers, occupational exposures and smoking, will be assessed in a case-referent study within the study base.

Kinetics of formation of exchanges and rejoining of breaks in human G0 and G2 lymphocytes after low-LET radiation.

PURPOSE: To study the kinetics of chromosomal break rejoining and exchange formation in human G0 and G2 lymphocytes after low-LET irradiation using the premature chromosome condensation (PCC) technique. METHODS: For the G0 experiments, isolated human lymphocytes were irradiated (1, 3 and 8 Gy) and immediate and delayed fusions (1, 3, 5, 8 and 24 h) were performed with CHO-cells, and 48-h cultures were set up simultaneously. Interphase and metaphase human chromosomes were hybridized with dual colour combination probes for chromosomes 2 and 4. For the G2 experiments, isolated lymphocytes from the same donor were cultured for 69 h, irradiated with 3 Gy 60Co gamma rays and fused with CHO cells immediately and after 1, 2 and 3 h. Chromatid breaks and exchanges were scored after Giemsa staining. RESULTS: In both G0 and G2 cells, exchanges were already observed at the first fusion and, at lower doses, their frequencies remained relatively stable over time. The exchange-type aberrations seen in G0 cells were mostly incomplete, especially in the first fusions, while the exchanges seen in metaphase were mostly complete. The frequency of complete exchanges increased by time during incubation, while the frequency of incomplete exchanges showed more variation and a general decline by time in the G0-PCC experiment. The number of breaks declined rapidly by time both in G0 and G2. The break rejoining rate was higher at 8 Gy than in the two lower doses in the G0-PCC. The overall aberration frequencies in G0 and G2 cells studied by PCC were higher than in the corresponding metaphase. The initial number of breaks in G2 was higher than in G0 and the break rejoining rate in the G2 was two-fold. CONCLUSIONS: The formation of complete exchanges in G0 is a delayed process. The incomplete exchanges appear unstable in G0. The decreasing proportion of incomplete exchanges and simultaneous increase in complete exchanges in G0-PCC indicates that formation of exchanges is not coordinated in time.

Localization of radiation-induced chromosomal breakpoints along human chromosome 1 using a combination of G-banding and FISH.

PURPOSE: To determine the exact location of radiation-induced chromosomal breakpoints along the euchromatic or heterochromatic regions: G-light and G-dark bands, respectively. MATERIALS AND METHODS: The distribution of radiation-induced chromosomal breakpoints was scored in human lymphocytes irradiated in vitro with 3 Gy of gamma-radiation. Image analysis was applied to combine G-banded and FISH-painted images of the human chromosome 1. RESULTS: A total of 195 chromosomal breakpoints in 176 cells with structural chromosomal aberrations was used for the present analysis. Radiation-induced breakpoints were found to be distributed randomly with respect to the p or q arms of chromosome 1 and specific band or band length, but more breakpoints were mapped to G-light than to G-dark bands, the difference being statistically significant. CONCLUSIONS: The results can well be interpreted in terms of concepts of existing models of nuclear architecture, chromatin structure and transcriptional activities of the chromatin, which can influence the induction of primary chromosomal aberrations by gamma-rays. Differential repair of randomly produced primary aberrations may also explain the non-random distribution of radiation-induced breakpoints.

Distribution of radiation-induced exchange aberrations in human chromosomes 1, 2 and 4.

PURPOSE: To examine the distribution of radiation-induced breakpoints in chromosomes 1, 2 and 4 both in relation to their DNA content and by localization of the breaks along each chromosome. MATERIAL AND METHODS: The work consisted of two studies, one with chromosomal aberrations found in persons after accidental exposure in Estonia in 1994 and another involving aberrations seen in in vitro-irradiated lymphocytes. Localization of breakpoints in painted chromosomes involved in complete exchange-type aberrations was conducted by applying a computerized measuring system on stored image-files. RESULTS AND CONCLUSIONS: The yield of exchanges in chromosomes 1, 2 and 4 in both studies was equal to that expected from their DNA content. In contrast, the breakpoint location of complete exchanges within these chromosomes was not random. Chromosomes 1 and 4 contained more breaks in the middle parts of the p and q arms, whereas breaks were observed more uniformly along chromosome 2. Complete exchanges, however, were very rare in the terminal regions of all three chromosomes, most probably resulting from limitations in the resolution of small painted pieces.

Domestic radon exposure and the frequency of stable or unstable chromosomal aberrations in lymphocytes.

PURPOSE: To clarify the relationship between domestic radon exposure and the occurrence of chromosomal aberrations, stable translocations especially, in peripheral blood lymphocytes. MATERIALS AND METHODS: The study comprised a total of 84 nonsmoking individuals, divided into three groups according to radon concentration measurements performed in their homes: low radon concentration (<100Bq/m3, mean 67Bq/m3), medium (200-400Bq/m3, mean 293Bq/m3) or high (>800Bq/m3, mean 1737Bq/m3). Minimum residence in the present low-rise house was 10 years. The groups were matched with regard to age, gender and medical exposure. Fluorescence in-situ hybridization (FISH) was performed using chromosome paints for chromosomes 1, 2 and 4; 1500 metaphases were scored from each individual. RESULTS: Equal frequencies of translocations and also other aberrations, e.g. dicentrics and complex rearrangements, were obtained in each group. Significant correlation of translocations with age was observed, and due to the high mean age (50 years) the genome-corrected frequency of translocations was high: about one translocation in 100 metaphases. CONCLUSIONS: Chronic exposure to high concentrations of domestic radon did not increase the rate of stable or unstable chromosomal aberrations in peripheral blood lymphocytes detected by FISH chromosome painting. A strong age effect was observed.

Persistence of translocations after accidental exposure to ionizing radiation.

PURPOSE: To assess the validity of translocations for retrospective biodosimetry using FISH chromosome painting of peripheral lymphocytes in repeated samples of people accidentally exposed to radiation. MATERIALS AND METHODS: Blood samples from five people exposed to mainly whole-body irradiation of gamma-rays from a radiation accident in Estonia in 1994 were taken at 2-4 month intervals. A total of eight samplings were carried out, including one directly after the accident. Fluorescence in situ hybridization with probes for chromosomes 1, 2 and 4 was performed on metaphase preparations from 48 h whole blood cultures; 1500 cells were scored from each individual per time point. RESULTS: Translocations remained relatively stable during 2 years after exposure in all subjects. A noticeable decrease in complete translocation yields and a significant decrease in incomplete translocations were observed in one person. In addition to whole-body exposure, he had also been exposed to partial-body irradiation. Due to the overall persistence of translocations, dose estimates were very similar throughout the 2 year period. A rapid decline in dicentric frequencies was noted during the first year after exposure. CONCLUSIONS: The results suggest that during 2 years the yield of translocations in peripheral lymphocytes remained at a constant level after whole-body exposure. This finding supports the use of translocations for retrospective dosimetry, at least within this relatively short period of follow-up. In the case of partial-body irradiation, however, the elimination of co-existing unstable aberrations reduced the translocation yield over time. Follow-up will be continued in order to determine the stability of translocations over longer times.

The incidence of cytogenetically abnormal rogue cells in peripheral blood.

PURPOSE: To compare the occurrence of cytogenetically abnormal rogue cells, characterized by a high frequency of chromosome-type aberrations, in people exposed to ionizing radiation and in non-exposed subjects. MATERIALS AND METHODS: Data on rogue cells from a total of nine cytogenetic studies on radiation-exposed populations and controls were collected from three laboratories in the United Kingdom, France and Finland. The studies were conducted on first-division metaphases of peripheral blood lymphocytes. Solid Giemsa-stained, G- or R-banded and FISH chromosome-painted material was included. RESULTS: Rogue cells were found both from controls and from exposed subjects. The highest incidence of these cells was observed in a control group of young trainees (1:400), whereas the lowest incidence of rogue cells (1:36 500) was demonstrated in a follow-up study of people accidentally exposed to high levels of ionizing radiation. Rogue cells were found to be distributed non-randomly among individuals; the highest individual frequency was 1 in 50 analysed metaphases. CONCLUSIONS: The origin of rogue cells is still unclear. The incidence of rogue cells showed a large variability between studies and individuals. No correlation between long-term radiation exposure and the occurrence of rogue cells was demonstrated. Although the presence of rogue cells in astronauts after a 6 month space flight may be attributable to high-LET radiation, the frequencies were not remarkable when compared with those in the other studies in this review.

Biodosimetry after accidental radiation exposure by conventional chromosome analysis and FISH.

A 137Cs source was stolen from a radioactive waste depository in Estonia on 21 October 1994 and kept in a private house for 4 weeks. This resulted in the death of one person, acute radiation injuries to four people and exposure of several other people to lower doses of radiation. Analysis of chromosomal aberrations in peripheral blood lymphocytes was used in the assessment of radiation exposure of 18 people involved in the accident. Dose estimation assessment based on the frequencies of dicentric chromosomes was performed both by the standard method and by considering possible dose protraction and non-uniform exposure. Considerable differences in dose estimates were obtained depending on the approach used, ranging from about 1 Gy to almost 3 Gy in the patients most heavily exposed. In view of the deterministic health effects observed in some of the subjects, it was concluded that the dose estimates involving information on dose protraction were more realistic than those obtained by comparison with the standard high dose-rate calibration curve. Chromosome painting analyses using fluorescence in situ hybridization, with a probe cocktail for chromosomes 1, 2 and 4 and centromere detection, were performed in parallel. Good agreement on dicentric chromosome frequencies was observed between the conventional and painting analyses. The frequencies of complete translocations were comparable with the frequencies of dicentric chromosomes. In addition to the complete translocations, a pronounced increase in the frequency of incomplete translocations was observed. Dose estimates performed on the basis of FISH translocation frequencies were consistent with the dicentric analysis.

Chromosomal instability in in vivo radiation exposed subjects.

PURPOSE: To investigate whether delayed chromosomal instability arises in human peripheral T lymphocytes exposed in vivo to gamma-irradiation. MATERIALS AND METHODS: Long-term cultures were established from lymphocytes obtained from subjects involved in the radiological accident in Estonia in 1994. Two individuals exposed to a high dose, one individual with low exposure and one apparently unexposed person were studied. Two Estonian controls not involved with the accident were also analysed. Cells were grown for 6-42 days and chromosomal aberrations were assessed from G-banded metaphases. In addition, FISH chromosome painting analysis was performed on short-term cultures established from whole blood. RESULTS: No obvious sign of chromosomal instability was observed in the in vivo follow-up of the frequencies of chromosomal aberrations in lymphocytes of radiation accident victims performed by the FISH technique (48 h cultures established at different time intervals after the exposure). However, when the lymphocytes were cultured long term in vitro, chromosomal instability was observed. There was no dose-response, and the appearance of chromosomally unstable cells in long-term cultures was also observed in a subject exposed to a dose of less than 0.1 Gy. Moreover, in contrast with previous findings, chromosomal instability was also observed in cells from non-exposed control individuals. The chromosomal changes observed in the controls were less complex than the aberrations in the cultures derived from individuals exposed to high doses. CONCLUSIONS: Chromosomal instability was observed in long-term cultures of donors with in vivo exposure to gamma-radiation. No dose-response was apparent. However, in contrast with previous findings, signs of chromosomal instability were observed also in long-term cultures from non-exposed controls. Further studies are needed to assess possible inter-individual differences in the induction of chromosomal instability.

Comparison of dose-response curves for chromosomal aberrations established by chromosome painting and conventional analysis.

PURPOSE: To establish 60Co gamma-ray dose-response curves for dicentrics and translocations visualized by chromosome painting and for dicentrics analysed after conventional solid staining. MATERIALS AND METHODS: Analysis of chromosomal aberrations was performed on peripheral blood lymphocytes obtained from 48 h old cultures of irradiated whole blood. Dicentrics were scored from Giemsa-stained preparations, and bi-coloured dicentrics and translocations after FISH painting of chromosomes 1, 2 and 4. RESULTS: Equal frequencies of complete dicentrics and translocations, where both members of the exchanges were seen, were observed in the chromosome painting analysis at all doses, resulting in similar calibration curves. Due to differences in scoring criteria, dicentrics scored in conventionally Giemsa-stained slides agreed better with data for total than for complete exchanges. Donor differences for translocations at the control level and at low doses were seen and large uncertainty surrounds the linear component of the dose-response for total translocations. CONCLUSIONS: Dose reconstruction of past exposures in cases of low doses is very dependent on the linear coefficient of the curve. Results indicate that total translocations would give less reliable dose estimates and therefore complete translocations are preferred.

Unstable and stable chromosomal aberrations in lymphocytes of people exposed to Chernobyl fallout in Bryansk, Russia.

Analyses of unstable and stable chromosomal aberrations in peripheral blood lymphocytes were used in the assessment of radiation exposure of residents of a village situated in the Chernobyl fallout-contamination zone of Bryansk, Russia. Blood samples were taken from subjects residing in villages with high (> 1100 kBq/m2 137 Cs; Mirnyi) and very low (< 37 kBq/m2 137 Cs; Krasnyi Rog) contamination, 7 years after the Chernobyl accident. The groups were matched by age, sex, smoking habits and previous medical radiological exposures. A total of 200 people (100 exposed, 100 controls) were analysed for the presence of unstable aberrations from Giemsa-stained slides. To study stable aberrations, chromosome painting analyses were performed on 100 subjects (50 exposed, 50 controls), using painting probes for chromosomes 1, 2 and 4 and a pancentromeric probe. People living in the contaminated area showed significantly higher rates of unstable chromosome-type aberrations but not chromatid-type aberrations in their lymphocytes, indicating radiation exposure as a causative factor for the observed difference. No significant differences were found in the aberration rates between the two areas by the chromosome painting method. The levels of chromosome exchanges were low in both populations, but consistently higher in Mirnyi compared with the control area. The magnitude of radiation exposure resulting from Chernobyl fallout was estimated on the basis of excess stable chromosomal aberrations in the lymphocytes of the Mirnyi population compared with the controls.

Inactivity of styrene in the mouse sperm morphology test.

Male F1-mice (C3H/He X C57B1/6J) were exposed to styrene by inhalation (150 and 300 ppm; 6 h per day; 5 days) or intraperitoneally (175, 350 and 700 mg/kg per day, 5 days). No statistically significant increase was detected in the frequency of abnormal sperm heads 3 weeks (spermatids exposed) or 5 weeks (late spermatogonia/early spermatocytes exposed) after the beginning of the exposures.