Methodik und Ergebnisse von Stoffwechseluntersuchungen beim Krebs

Ohne ZusammenfassungMit 13 Textabbildungen     

Enhancement of benzo[a]pyrene-induced sister chromatid exchanges in lymphocytes from cigarette smokers occupationally exposed to asbestos

The frequencies of base-line and benzo[a]pyrene [(BP) CAS 50-38-8]-induced sister chromatid exchanges (SCE) were measured in peripheral blood lymphocytes from 22 male asbestos-exposed workers and 10 nonexposed workers of comparable age. A clear association between cigarette smoking and asbestos exposure in the sensitivity of lymphocytes to BP was observed. Among asbestos-exposed workers, lymphocytes from those who smoked cigarettes were significantly more susceptible to the induction of SCE by in vitro exposure to BP (P = .01) than were lymphocytes from nonsmokers. Active smoking elevated the base-line SCE frequency in both asbestos-exposed and nonexposed workers (P = .001), and an interaction between smoking and asbestos in the production of base-line SCE was suggested (P = .07). Asbestos exposure alone was not associated with an enhanced susceptibility to the induction of SCE by BP or with an elevation of base-line SCE. Increased age was associated with an increase in SCE inducibility by BP (P = .01), and a history of smoking was marginally associated with SCE inducibility by BP (P = .07). These findings support the hypothesis that an increased susceptibility of asbestos-exposed individuals to polyaromatic hydrocarbon-induced cancer results from an enhanced sensitivity to the induction of genetic damage rather than to an asbestos-induced differential cellular metabolic capacity.     

Pulmonary function in workers exposed to low levels of fuel-oil ash

Previously, we reported significant lung function changes after exposure to fuel-oil ash during a boiler overhaul in which median PM10 and vanadium concentrations were 2.9 mg/m3 and 11.9 micrograms/m3, respectively. In this study, we examined prospectively 18 boilermakers involved in the short-term, partial overhaul of a large, oil-fired boiler where occupational exposures to PM10 and metals were relatively low. Vanadium and PM10 exposure levels were measured before and during boiler work. For PM10, median exposure before and during boiler work was 0.5 and 0.6 mg/m3, respectively. For vanadium, median exposure before and during boiler work was 1.0 and 12.7 micrograms/m3, respectively, comparable with the results of our previous study. Spirometric (PFT) testing was done three times: first day on the job (PFT1), end of overhaul (PFT2), and 2 weeks post-overhaul (PFT3). Spirometry results were analyzed using repeated measures analysis of variance. No significant differences were found. Boilermakers working on a short-term overhaul of an oil-fired boiler exhibited no significant change in any lung function parameter comparing pre-, during, and 2 weeks post-exposure. The comparatively low levels of exposure to PM10 and vanadium observed during boiler work, the short duration of the overhaul, and the healthy worker effect are possible explanations for these results.     

Assessment of coke oven emissions exposure among coking workers

Coking workers are regularly exposed to coke oven emissions, which consist primarily of polycyclic aromatic hydrocarbons and volatile organic compounds. This study measured the workers' exposure to the benzene soluble fraction of total particulates (BSF). The study population consisted of 88 coking workers as an exposure group and 59 referents. Personal breathing-zone samples of BSF and total particulates were taken from all study subjects for 3 consecutive days. The highest BSF concentrations were found among the topside oven workers (geometric mean; range) (microgram/m3): lidman (515; 72-18, 181), tar chaser (432; 51-4334), and larry car operator (185; 55-649). The lowest was 7 micrograms/m3 in the referents. Among the samples at the topside oven 84% exceeded the Occupational Safety and Health Administration standard (150 micrograms/m3 BSF). The percentage of BSF in total particulates varied across job classifications, ranging from 0.3% in wharfmen to 24% in tar chasers. Area sampling indicated that the BSF concentration at the topside area was sixtyfold higher than that at the administrative area, which was approximately 2 km from the coke oven plant.     

Correlates of fitness for duty in hazardous materials firefighters

BACKGROUND AND METHODS: From a statewide medical examination program, we identified firefighters who were deemed unfit for duty by attending physicians (ATTENDING FAIL, n=9) and those who would have been disqualified by the application of selected numerical criteria from the 1997 National Fire Protection Association (NFPA) guidelines (NFPA FAIL, n=27) and criteria from a Medical Workshop (WORK FAIL, n=16). The subjects who were unfit for duty or failed numerical criteria were compared with those who were fit for duty and passed all objective criteria (FIT group, n=302). All subjects were given an overall morbidity rating by a board certified internist. Comparisons on two surrogate measures of fitness, VO(2) max predicted and predicted coronary heart disease (CHD) risk, were also performed. RESULTS: We found a significant tendency towards worse results (e.g. higher blood pressure or lower spirometric function) among the three FAIL groups compared with the FIT group. The FAIL groups shared only a small overlap, however, with the firefighters with the highest morbidity ratings, lowest predicted VO(2) max, and highest CHD risks. Increasing morbidity was associated with higher age, lower spirometric function, lower predicted VO(2) max, increasing cholesterol, greater BMI, and higher predicted 10 year CHD risk. CONCLUSIONS: Although the presence of a single serious or poorly controlled condition may render an individual unfit for safe performance as a firefighter, examination of our cohort suggests that multiple risk factor models or overall clinical assessments are superior means of identifying firefighters with poor health status and increased CHD risk.     

Inhaled environmental combustion particles cause myocardial injury in the Wistar Kyoto rat.

Epidemiologists have associated particulate matter (PM) air pollution with cardiovascular morbidity and premature mortality worldwide. However, experimental evidence demonstrating causality and pathogenesis of particulate matter (PM)-induced cardiovascular damage has been insufficient. We hypothesized that protracted, repeated inhalation by rats of oil combustion-derived, fugitive emission PM (EPM), similar in metal composition to selected sources of urban air PM, causes exposure duration- and dose-dependent myocardial injury in susceptible rat strains. Zinc was the only primary water-leachable/bioavailable element of this EPM. Male Sprague-Dawley (SD), Wistar Kyoto (WKY), and spontaneously hypertensive (SH) rats were exposed nose-only to EPM (2, 5, or 10 mg/m(3), 6 h/day for 4 consecutive days or 10 mg/m(3), 6 h/day, 1 day/week for 4 or 16 consecutive weeks). Two days following the last EPM exposure, cardiac and pulmonary tissues were examined histologically. The results showed that particle-laden alveolar macrophages were the only pulmonary lesions observed in all three rat strains. However, WKY rats exposed to EPM (10 mg/m(3) 6 h/day, 1 day/week for 16 weeks) demonstrated cardiac lesions with inflammation and degeneration. To further characterize the nature of EPM-associated lesions, more rigorous histopathological and histochemical techniques were employed for WKY and SD rats. We examined the hearts for myocardial degeneration, inflammation, fibrosis, calcium deposits, apoptosis, and the presence of mast cells. Decreased numbers of granulated mast cells, and multifocal myocardial degeneration, chronic-active inflammation, and fibrosis were present in 5 of 6 WKY rats exposed to EPM for 16 weeks. None of these lesions were present in WKY exposed to clean air. EPM-related cardiac lesions were indistinguishable from air-exposed controls in SD and SH rats. This study demonstrates that long-term inhalation exposures to environmentally relevant PM containing bioavailable zinc can cause myocardial injury in sensitive rats. These findings provide supportive evidence for the epidemiological associations of cardiovascular morbidity and ambient PM.     

A case-control study of cytochrome P450 1A1, glutathione S-transferase M1, cigarette smoking and lung cancer susceptibility (Massachusetts, United States)

Cytochrome P450 1A1 (CYP1A1) and glutathione S-transferase M1 (GSTM1)genetic polymorphisms are involved in the activation and detoxification ofchemical carcinogens found in tobacco smoke; thus they may influence hostsusceptibility to lung cancer. In this study at Massachusetts GeneralHospital (Boston, MA, USA) of 416 cases and 446 controls (mostly White) weevaluated the association between the CYP1A1 MspI and GSTM1 polymorphisms andlung cancer risk, and their interaction with cigarette smoke. The CYP1A1 MspIheterozygous genotype was present in 18 percent of cases and 16 percent ofcontrols, and one percent of cases and controls were CYP1A1 MspI homozygousvariant. The GSTM1 null genotype was detected in 54 percent of cases and 52percent of controls. After adjusting for age, gender, pack-years of smoking,and years since quitting smoking, while neither the CYP1A1 MspI heterozygousgenotype alone nor the GSTM1 null genotype alone were associated with asignificant increas e in lung cancer risk, having both genetic traits wasassociated with a twofold increase in risk (95 percent confidence interval[CI] = 1.0-3.4). Our data did not provide enough evidence for a substantialmodification of the effect of pack-years on lung cancer risk by the CYP1A1MspI and GSTM1 genotypes. However, limitations of our study preclude aconclusion about this potential interaction.     

Association of Air Pollution with Hospital Outpatient Visits in Beijing

Data collected at a community-based hospital in Beijing, China, were analyzed in an assessment of the association of air pollution with daily outpatient visits. Total suspended particle (TSP) measurements were available for 210 d (mean, 388 μg/m³; maximum, 1 255 μg/m³), and sulfur dioxide (SO₂) measurements were available for 2 d (mean, 119 μg/m³; maximum, 478 μg/m³). The average number of daily hospital outpatient visits was 1 386; approximately 8.5% of these visits were to the surgery department, 7.9% were to the pediatrics department, and 20.6% were to the internal medicine department. A large increase in nonsurgery outpatient visits was observed in association with increases in both SO₂, and TSP in linear regression models, after adjusting for temperature, humidity, season, and day of the week. The estimated effects (in which the most polluted days were compared with the least polluted days) on nonsurgery outpatient visits were increases of 20% (SE = 5%) and 17% (SE = 4%) in association with increases in SO₂ and TSP, respectively. In a department-specific analysis, the association was found to be 1.5- to 2.0-fold stronger for pediatrics and internal medicine visits than for other types of visits. The separate associations of SO₂ and TSP with internal medicine visits remained statistically significant when both SO₂, and TSP were considered simultaneously and when adjustment was made for surgery visits. SO₂ and TSP were found to be significant, independent predictors of internal medicine visits in both winter and summer. The association between outpatient visits and air pollution appeared to be stronger in summer than in winter, although the summer daily mean SO₂ concentration was only 17 μg/m3 (maximum, 51 μg/m³). These data, together with data obtained in previous studies, provide coherent evidence that current air-pollution levels in Beijing are associated with adverse health outcomes, and they also suggest that air pollution in Beijing needs to be controlled more effectively.