The relationship of bone marrow type and microvasculature to the microdistribution and local dosimetry of plutonium in the adult skeleton

Most plutonium-induced bone tumors in beagles arise in trabecular bone sites surrounded by hematopoietic tissue. The microvasculature and the relative incorporation of 241Pu (a low energy beta emitter) on trabecular bone surfaces from red and fatty marrow sites were studied in the adult beagle. The vascular volume, as determined by India ink perfusion, was about 16% in the red marrow and about 2% in the fatty marrow. The red marrow has large vascular sinusoids with a discontinuous endothelial lining whereas fatty marrow has a closed capillary bed. Plutonium concentrations on bone surfaces of red marrow sites are about 0.43 pCi/cm2/nCi/kg of injected dosage, a factor of eight greater than at fatty marrow sites (0.053 pCi/cm2/nCi/kg). The differences in the bone marrow microvasculature between red and fatty marrow help to explain differences in plutonium incorporation and local bone physiology in these skeletal sites. These observations may relate to the nonuniform distribution of plutonium-induced osteosarcomas observed in adult, long-lived mammals.     

Immunomodulatory effects of mineral fibres in occupationally exposed workers

In the context of a large-scale molecular epidemiology study, the possible immunomodulatory effects of mineral fibres, in workers occupationally exposed to asbestos, rockwool and glass fibres, were examined. In each plant, 61, 98 and 80 exposed workers and 21, 43 or 36 control clerical subjects, respectively, were recruited. In the case of the asbestos-exposed subjects, an additional town-control group of 49 people was included. Evidence of pulmonary fibrosis was found in 42% of the asbestos-exposed workers, while evidence of pleural fibrosis was found in 24%. The asbestos-exposed cohort had significantly decreased forced vital capacity of lungs as well as forced expiratory volume per first second. Our findings indicate that exposure to all three types of fibres examined modulates to different degrees the immune response. Suppression of T-cell immunity and to a lesser extent, B-cell immunity was found in the case of workers from a former asbestos cement plant, while stimulation of T-cell response was observed in rockwool workers, and stimulation of T- and B-cell response was seen in glass fibre workers. Depression of the percentage of lymphocyte subpopulation of CD 16+56 (natural killer cells) in peripheral blood was found in glass fibre workers. Statistical analysis showed increased levels of proinflammatory cytokines (IL-6 asbestos; IL-8 all three fibres), expression of adhesion molecule L-selectin on granulocytes and monocytes (asbestos), levels of soluble adhesion molecules (SAMs) in sera (ICAM-1 all three fibres; E-selectin glass fibres), increased levels of immunoglobulin E (asbestos and rockwool) and elevated expression of activation markers on eosinophils (CD66b asbestos, glass fibres; CD69 asbestos). Significant correlations were observed between lymphocyte proliferation and markers of DNA damage and repair. Increased levels of proinflammatory cytokines, SAMs, immunoglobulin E and elevated expression of activation markers on eosinophils was found in people with symptoms of hypersensitivity and an elevated inflammatory status.     

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.     

Cytogenetic biomonitoring of workers from laboratories of clinical analyses occupationally exposed to chemicals

A cytogenetic monitoring study was carried out on a group of workers in clinical analysis laboratories to investigate the risk of occupational exposure to chronic low levels of chemicals.Thirty-four clinical laboratories have been involved in the study. In these laboratories, toxicants and analytical procedures utilized have been characterized. The individual occupational exposure of workers was assessed by use of a questionnaire concerning the chemical substances utilized. About 300 different chemicals have been identified.Cytogenetic analyses (chromosomal aberration and micronucleus tests) were carried out on a strictly selected group of 50 workers enrolled from these laboratories and compared to 53 controls (healthy blood donors) matched for gender and age.The exposed group shows a significantly higher frequency of genetic damage than the control group. Both chromatid and chromosome aberration frequencies in workers appear significantly higher than in controls. Similarly, comparison between micronucleated cells rates of exposed and unexposed groups show significantly higher frequencies of binucleated cells with micronucleus (BNMN) and of total micronuclei (MN tot) in workers than in controls.     

Cytogenetic effects in workers occupationally exposed to tobacco dust

Tobacco dust mainly contains nitrosamines, which are readily absorbed by the body tissues like skin, respiratory epithelium, and mucous membrane of mouth, nose and intestines. Exposure to tobacco dust is known to affect the respiratory tracts in humans. In the present study, cytogenetic effects of exposure to tobacco dust are evaluated in 154 male tobacco factory workers and 138 age and sex matched controls by analysing chromosomal aberrations in their peripheral blood lymphocytes. The workers were in the age group of 20-55 years and were employed in the tobacco processing factory for 1-32 years. Heparinised blood samples were collected from workers and control subjects and lymphocyte cultures were carried out by using standard technique. Slides were prepared and 150 metaphases were screened for each sample for various structural and numerical types of abnormalities. A statistically significant increase was observed in the frequencies of chromosomal aberrations in non-smoking and smoking exposed groups when compared to the respective controls. An increase in the frequencies of chromosomal aberrations was also observed with increase in years of service in the exposed subjects.     

Cytogenetic biomonitoring of workers from laboratories of clinical analyses occupationally exposed to chemicals

A cytogenetic monitoring study was carried out on a group of workers in clinical analysis laboratories to investigate the risk of occupational exposure to chronic low levels of chemicals.Thirty-four clinical laboratories have been involved in the study. In these laboratories, toxicants and analytical procedures utilized have been characterized. The individual occupational exposure of workers was assessed by use of a questionnaire concerning the chemical substances utilized. About 300 different chemicals have been identified.Cytogenetic analyses (chromosomal aberration and micronucleus tests) were carried out on a strictly selected group of 50 workers enrolled from these laboratories and compared to 53 controls (healthy blood donors) matched for gender and age.The exposed group shows a significantly higher frequency of genetic damage than the control group. Both chromatid and chromosome aberration frequencies in workers appear significantly higher than in controls. Similarly, comparison between micronucleated cells rates of exposed and unexposed groups show significantly higher frequencies of binucleated cells with micronucleus (BNMN) and of total micronuclei (MN tot) in workers than in controls.     

Clastogenic activity in urine of workers occupationally exposed to pesticides

Genotoxicity in the urine of orchardists occupationally exposed to pesticides was investigated. Urine samples were obtained during pre-spraying and spraying periods from 22 non-smoking orchardists who spray large amounts of pesticides during the fruit growing season. For comparison purposes, urine was collected from 11 non-smoking personnel at an agricultural research station located near the application site and from 21 non-smoking individuals (reference controls) in a non-agricultural area. Organic material was isolated from urine by preparative reversed-phase high-pressure liquid chromatography, and assayed for clastogenic activity using Chinese hamster ovary cells. Urine samples collected during the pre-spraying period showed no significant differences in clastogenic activity compared to that found for the reference control group. However, clastogenic activity of urine specimens collected during the spraying period was significantly elevated (p less than 0.001) for the highly-exposed orchardists, but not for the research station personnel. Clastogenicity of orchardists' urine was observed within 8 h of pesticide application.     

Mortality risk of cardiovascular diseases for occupationally exposed workers

Results of the risk analysis of mortality from ischemic heart disease (IHD) in the cohort of Mayak nuclear workers (18763 individuals) first employed in 1948-1972, with follow-up to 31.12.2005, were summarized. The mortality risk of IHD in the cohort of Mayak workers depended on the non-radiation factors such as gender, age, calendar period, smoking, alcohol consumption, arterial hypertension, body mass index. There was no statistically significant relationship between mortality from 1HD and total external dose. The risk of mortality from IHD was significantly higher for workers exposed to the total absorbed dose to liver > 0.025 Gy from internal alpha-radiation. There was a significantly increasing trend (ERR/Gy) of the IHD mortality with the total absorbed dose to liver from internal alpha-radiation due to incorporated plutonium. However, there was a decreasing trend of ERR/Gy with restriction of the follow-up to Ozyorsk and adjustment for the external dose.     

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.     

Immunological profiles in workers occupationally exposed to inorganic mercury.

Forty-one male mercury-exposed workers were examined for the serum concentration levels of immunoglobulins (IgG, IgA, IgM), alpha-1-antitrypsin (A1AT), alpha-2-macroglobulin (A2M), ceruloplasmin (CPL) and orosomucoid (ORO). In the period preceding this investigation the mercury concentrations in workplace air ranged from 0.106 to 0.783 mg.m-3, the range of urinary mercury concentrations was from 0.029 to 0.545 mg.1(-1). All but two (IgG and A1AT) of the immune parameters tested were at the levels that were evidently higher than those found in a control group of 55 workers matched by age who lived in a relatively clean area. The percentage of individuals with no value out of the range of normal physiological limits was in the controls almost 80%, in the exposed 36.6% only. These findings confirm the literature data which show that an inhalation exposure to inorganic mercury may evidently have a stimulating effect on some serum proteins in humans.     

Mitochondrial DNA mutations in individuals occupationally exposed to ionizing radiation

Mutations in a 443-bp amplicon of the hypervariable region HVR1 of the D-loop of mitochondrial DNA (mtDNA) were quantified in DNA extracted from peripheral blood samples of 10 retired radiation workers who had accumulated external radiation doses of >0.9 Sv over the course of their working life and were compared to the levels of mutations in 10 control individuals matched for age and smoking status. The mutation rate in the 10 exposed individuals was 9.92 x 10(-5) mutations/ nucleotide, and for the controls it was 8.65 x 10(-5) mutations/ nucleotide, with a procedural error rate of 2.65 x 10(-5) mutations/nucleotide. No increase in mtDNA mutations due to radiation exposure was detectable (P = 0.640). In contrast, chromosomal translocation frequencies, a validated radiobiological technique for retrospective dosimetric purposes, were significantly elevated in the exposed individuals. This suggests that mutations identified through sequencing of mtDNA in peripheral blood lymphocytes do not represent a promising genetic marker of DNA damage after low-dose or low-dose-rate exposures to ionizing radiation. There was an increase in singleton mutations above that attributable to procedural error in both exposed and control groups that is likely to reflect age-related somatic mutation.     

Mayak worker study: an improved biokinetic model for reconstructing doses from internally deposited plutonium

The plutonium production facility known as the Mayak Production Association was put into operation in June 1948. A high incidence of cancer in the Mayak workers has been related to the level of exposure to plutonium, but uncertainties in tissue doses have hampered development of dose-risk relationships. As part of an effort to improve dose estimates for these workers, the systemic biokinetic model for plutonium currently recommended by the International Commission on Radiological Protection (ICRP) has been modified to reflect recently developed data and facilitate interpretation of case-specific information. This paper describes the proposed model and discusses its implications for dose reconstruction for the Mayak workers.     

Sister chromatid exchange in pathology staff occupationally exposed to formaldehyde

Sister chromatid exchange (SCE) was measured in peripheral lymphocytes of 90 workers from 14 hospital pathology departments in Israel who were occupationally exposed to formaldehyde (FA) and of 52 unexposed workers from the administrative section of the same hospitals. The mean exposure period to FA was 15.4 years (range 1-39). The results of SCEs are expressed in two variables: (a) mean number of SCEs per chromosome and (b) proportion of high frequency cells (cells with more than eight SCEs). A high correlation was found between these two variables. The adjusted means of both SCEs variables were significantly higher among the exposed compared with that of the unexposed group (P<0.01). Adjustment was made for age, sex, smoking habits, education workers and origin. Evaluation of the influence of years of exposure on the frequency of SCEs showed that the two variables of SCEs were higher among those who were exposed to FA for 15 or more than among those with less than 15 years of exposure. Concerning levels of exposure, both variables of SCEs were the same in the low and in the high levels of exposure sub-groups. However, among the smokers, both variables of SCEs were higher in the high exposure sub-group than in the low exposure sub-group.Our finding of a significant increase of SCEs frequency in peripheral lymphocytes in pathology staff indicates a potential cytogenetic hazard due to FA exposure. We conclude that our data indicate that FA is mutagenic to humans.     

Micronuclei frequency in lymphocytes of individuals occupationally exposed to pesticides.

Pesticides have been widely used in developing countries over the years. A large amount of these remains in the environment and organisms. Pesticide pollution is detrimental to human health. The effects can be seen on a short or a long-term basis and the symptoms can vary from headache to cancer. Only a minority of studies focuses on their genotoxic effect. This study assesses the genotoxic effect of the pesticides used at banana-packaging plants with binucleate micronuclei assay using cultured lymphocytes. The studied population included 32 exposed and 37 unexposed women from Costa Rica. There is no significant difference between the two groups. However, women who worked at the packaging plant and had stillbirths or spontaneous abortions were 1.45 times more (alpha = 0.06) likely to have an increased micronuclei frequency than their coworkers who lacked those disorders; this may indicate genetic susceptibility. In vitro pesticides studies and susceptibility biomarkers are needed to identify subgroups with higher risks.