Chromosomal aberrations and sister-chromatid exchanges in tool and die workers

Because tool and die workers are exposed to a number of potentially genotoxic agents, including mutagenic metals, polyaromatic hydrocarbons, and nitrosamines, and may be at increased cancer risk, the present study was undertaken to test whether chromosomal damage in peripheral blood cells is associated with work in the tool and die industry. Lymphocyte cultures were established from 27 tool and die fabrication workers from one manufacturing plant who had worked in the trade for more than 15 years. 15 of these workers also had some form of malignancy at the time of the study, but had not been treated with radiation or chemotherapies that could themselves induce chromosomal damage. The frequencies of chromosomal aberrations and sister-chromatid exchanges (SCEs) were measured in workers and the data compared with those of a control group consisting of 7 non-fabrication workers from the same plant and 8 age-matched community controls. In addition, the relative rates of lymphocyte proliferation were estimated for each group by analyzing the percentages of first-, second- and third-division mitotic cells after 72 h of culture. The results of the chromosomal studies show that tool and die workers have significantly increased frequencies of aberrations whether engaged in fabrication work or not, compared to control subjects. The frequency of SCEs and the frequencies of 1st, 2nd and 3rd division figures are not different among the study groups. Among workers who are engaged in fabrication, including those who are cancer patients, the frequency of more complex aberrations (i.e., interstitial deletions and small acentric fragments) is increased. In a five-year follow-up of these workers, 2 of the 13 workers with these aberrations developed some form of colon cancer. Whether the presence of interstitial deletions and small acentric fragments is related to the occupation of these workers, or is tangentially related to the development of cancer, is presently under consideration.     

Lung cancer in Mayak workers

The cohort of nuclear workers at the Mayak Production Association, located in the Russian Federation, is a unique resource for providing information on the health effects of exposure to plutonium as well as the effects of protracted external dose. Lung cancer mortality risks were evaluated in 21,790 Mayak workers, a much larger group than included in previous evaluations of lung cancer risks in this cohort. These analyses, which included 655 lung cancer deaths occurring in the period 1955-2000, were the first to evaluate both excess relative risk (ERR) and excess absolute risk (EAR) models and to give detailed attention to the modifying effects of gender, attained age and age at hire. Lung cancer risks were found to be significantly related to both internal dose to the lung from plutonium and external dose, and risks were described adequately by linear functions. For internal dose, the ERR per gray for females was about four times higher than that for males, whereas the EAR for females was less than half that for males; the ERR showed a strong decline with attained age, whereas the EAR increased with attained age until about age 65 and then decreased. Parallel analyses of lung cancer mortality risks in Mayak workers and Japanese A-bomb survivors were also conducted. Efforts currently under way to improve both internal and external dose estimates, and to develop data on smoking, should result in more accurate risk estimates in the future.     

Lung cancer in nuclear workers of Mayak

Lung cancer mortality was analyzed among 4279 nuclear workers of the Mayak facilities in the former Soviet Union, who were exposed to chronic irradiation both externally and internally from incorporated plutonium. The analysis was carried out in terms of a relative risk model. It was shown that an earlier estimate of the excess relative risk for lung cancer, that exceeds the value employed by ICRP by a factor of roughly 2, as well as an earlier estimated latency period of 24 years for lung cancer induction were the result of the numerical procedure chosen. In another recently published case control study, a purely quadratic, threshold-type dose response to incorporated plutonium was deduced. In the present calculations, no evidence for a departure from linearity in dose response was suggested. Principal aim of this study has been the comparison to methods used in the earlier cohort analysis. More detailed risk modelling on the basis of the most recent follow-up will be required.     

Antibody arrays--an emerging tool in cancer proteomics

Cancer is a result of complex changes that occur in normal cells as they transform to become malignant and further when they become metastatic. These changes are not a consequence of a single protein but rather involve multiple proteins that function in pathways and networks. Thus, profiling cancer-associated changes requires simultaneous measurement of many proteins in a single sample. Identifying these changes may lead to the discovery of cancer-associated biomarkers that may assist in diagnosis, prognosis, patient monitoring and possibly for therapeutic purposes. Antibody arrays are a relatively new technology that enables one to perform multiplex high-throughput protein expression profiling. This review describes current technologies in antibody array and assay design, and presents a survey of the current literature on the use of these arrays in cancer research.     

Ant workers die young and colonies collapse when fed a high-protein diet

A key determinant of the relationship between diet and longevity is the balance of protein and carbohydrate in the diet. Eating excess protein relative to carbohydrate shortens lifespan in solitary insects. Here, we investigated the link between high-protein diet and longevity, both at the level of individual ants and colonies in black garden ants, Lasius niger. We explored how lifespan was affected by the dietary protein-to-carbohydrate ratio and the duration of exposure to a high-protein diet. We show that (i) restriction to high-protein, low-carbohydrate diets decreased worker lifespan by up to 10-fold; (ii) reduction in lifespan on such diets was mainly due to elevated intake of protein rather than lack of carbohydrate; and (iii) only one day of exposure to a high-protein diet had dire consequences for workers and the colony, reducing population size by more than 20 per cent.     

The HOME microscope workstation. A new tool for cervical cancer screening.

The Highly Optimized Microscope Environment (HOME) is a computerized microscope design for assisting pathologists and cytotechnologists in routine clinical tasks. The prototype system consists of an IBM PC-compatible computer and a light microscope in which a built-in high-resolution computer display image is super-imposed on the optical image of the specimen. Also, an encoding stage and objective turret encoder are used to provide continuous monitoring of the stage coordinates and microscope magnification to the computer. This allows any position on the stage to be uniquely defined. Software, written in C language and running under the MS-DOS/MS-Windows environment, is controlled by means of a mouse-driven cursor. A specific application has been developed for cervical cancer screening, taking into account the needs and constraints of microscopists performing this task. Informatics tools offered by the HOME system provide them with precise flagging and relocation of objects on the slide, control of the scanning pathway, and ability to write and print the report directly through the microscope. The computer files generated by microscopic examination are stored and contain information available for quality control assessment and laboratory management.     

Teaching cancer cells to die

Tumor cells have evolved numerous mechanisms to thwart apoptosis. As our understanding of the machinery which regulates cell-death evolves, these apoptotic defects have fallen into the crosshairs of cancer drug developers. The issues raised in exploiting these alterations for therapeutic benefit are discussed.     

Cancer mortality in metal workers.

Age-standardized proportional mortality ratios (PMRs) were calculated for 10 036 metal workers in British Columbia with the use of information on cause of death and occupation recorded in death registrations from 1950 to 1978. Metal workers were found to have a significantly increased risk of death from lung cancer (PMR = 134). In addition, certain occupational groups of metal workers were found, for the first time, to be at increased risk of death from other types of cancer; these included leukemia (PMR = 356) and cancer of the rectum (PMR = 248) in metal mill workers, Hodgkin''s disease in welders (PMR = 242) and multiple myeloma in machinists (PMR = 209).     

Historical review of occupational exposures and cancer risks in medical radiation workers

Epidemiological studies of medical radiation workers have found excess risks of leukemia, skin and female breast cancer in those employed before 1950 but little consistent evidence of cancer risk increases subsequently. Occupational radiation-related dose-response data and recent and lifetime cancer risk data are limited for radiologists and radiologic technologists and lacking for physicians and technologists performing fluoroscopically guided procedures. Survey data demonstrate that occupational doses to radiologists and radiologic technologists have declined over time. Eighty mostly small studies of cardiologists and fewer studies of other physicians reveal that effective doses to physicians per interventional procedure vary by more than an order of magnitude. For medical radiation workers, there is an urgent need to expand the limited information on average annual, time-trend and organ doses from occupational radiation exposures and to assess lifetime cancer risks of these workers. For physicians and technologists performing interventional procedures, more information about occupational doses should be collected and long-term follow-up studies of cancer and other serious disease risks should be initiated. Such studies will help optimize standardized protocols for radiologic procedures, determine whether current radiation protection measures for medical radiation workers are adequate, provide guidance on cancer screening needs, and yield valuable insights on cancer risks associated with chronic radiation exposure.     

Leukaemia and thyroid cancer in emergency workers of the Chernobyl accident:

This work focuses on the direct epidemiological assessment of the risks of radiation-induced leukaemia and thyroid cancer in emergency workers (EW) after the Chernobyl accident. The Russian National Medical Dosimetric Registry (RNMDR) contains data for 168 000 EW as of January 1, 1996. The analysis relates to 48 leukaemias and 47 thyroid cancers, diagnosed and verified. Radiation risks are estimated by comparing the EW data with national data for a male population of the same age distribution. For leukaemia, an excess relative risk per Gy (ERR/Gy) of 4.30 (95% CI: 0.83, 7.75) is obtained, while the excess absolute risk per 10⁴ person-years (PY) Gy (EAR/10⁴ PY Gy) is found to be 1.31 (95% CI: 0.23, 2.39); for thyroid cancer an ERR/Gy of 5.31 (95% CI: 0.04, 10.58) is obtained, and an EAR/10⁴ PY Gy of 1.15 (95% CI: 0.08, 2.22).     

Lung cancer in Mayak workers: interaction of smoking and plutonium exposure

Lung cancer mortality among 5058 male workers of the Mayak Production Association has been analyzed with emphasis on the interaction of smoking and radiation exposure by using the two-step clonal expansion (TSCE) model of carcinogenesis. The cohort consists of all Mayak workers with known smoking status, who were employed in the period 1948–1972, and who either had the plutonium concentration in urine measured or who worked in the reactors, where plutonium exposure was negligible. Those who died during the first two years after the first urine sampling were excluded. The follow-up extended until the end of 1998. During this time, 2176 workers died, including 244 lung cancer cases. Mayak workers were exposed to external (gamma and neutron) radiation, and in the radiochemical and plutonium plants to plutonium. In the preferred TSCE model, internal radiation and smoking act on the clonal expansion of pre-carcinogenic clones. Assuming a plutonium radiation weighting factor of 20, the excess relative risk per lung dose was estimated to be 0.11 (95% CI: 0.08; 0.17) Sv⁻¹. Most of the lung cancer deaths are found to be due to smoking. The second main factor is the interaction of smoking and internal radiation. The model is sub-multiplicative in relative risks due to smoking and radiation. In a multiplicative version of the TSCE model, internal radiation acts on initiation and transformation rates. This model version agrees with conventional epidemiological risk models, because it also suggests a higher risk estimate than the preferred TSCE model. However, it fits the data less well than the preferred model. An erratum to this article can be found at