Misleading "New Insights into the Chrysotile Debate".

Although there is no dispute among independent scientists about the carcinogenic and fibrogenic effects of chrysotile, the asbestos industry has been continuously and successfully acting to cast doubts on its harm. Another approach including asbestos insurance entities is to refuse compensation by raising the bar and fight criminal prosecution for asbestos-related diseases by the help of paid scientists. A recent publication on asbestos fibre burden in human lungs fits well in this context. The claim that chrysotile fibres are biopersistent in human lung is not based on the data provided by these authors, and, additionally, exhibits serious inconsistencies and obvious mismeasurements and significant methodological problems. The conclusion of the authors that fibre analysis of workers' lungs "is of high significance for differential diagnosis, risk assessment and occupational compensation" is unfounded and reprehensible. Also the available literature, the statements of the WHO, IARC, other decisive independent international organizations, and all our experience provide abundant evidence to the contrary. Note, the method is generally restricted to research only and is not recognized for diagnostic purpose and compensation in any other country. In conclusion, fibre counting in lung tissues should not be used to estimate former exposure to chrysotile comprising c. 94 % of applied asbestos in Germany. The authors claim that the analyses can improve the compensation rates in Germany. However, the opposite has been the case; it significantly worsens the non-justified denial of well-substantiated compensation claims.

[Lung Cancer as an Occupational Disease]. / Lungenkrebs als Berufskrankheit.

Lung cancer is one of the most frequently encountered cancer types. According to the latest WHO data, about 10 % of this disease are due to occupational exposure to cancerogens. Asbestos is still the number one carcinogen. Further frequent causes include quarz and ionizing radiation (uranium mining). Probable causes of the disease can be identified only with the help of detailed occupational history taken by a medical specialist and qualified exposure assessment. Without clarifying the cause of the disease, there is neither a correct insurance procedure nor compensation for the victim, and furthermore, required preventive measures cannot be initiated.

[Do advers health effects of chrysotile and amphibole asbestos differ?]. / Gibt es Unterschiede in den gesundheitsschädlichen Wirkungen von Chrysotil- und Amphibol-Asbest?

Due to the current query whether the predominantly used chrysotile (white) asbestos comprises health risks we performed a literature search including in vitro and animal experiments as well as epidemiological studies.As shown by epidemiological studies chrysotile causes less pleural fibrosis and mesotheliomas when compared with other asbestos types. However, its otherwise inflammatory, toxic, carcinogenic, and fibrosis-inducing effects correspond to those of other occupationally relevant asbestos types. This is based on clinical, animal as well as on in-vitro findings. This means that denying a causal relationship, e. g. in a case with lung fibrosis (= asbestosis) or lung cancer with an asbestos load of 25 fiber-years in the absence of identification of a significant concentration of asbestos fibers or asbestos bodies in the lung (see so-called "hit and run" phenomenon), contradicts the medical-scientific knowledge.

[Diagnosing and expertizing asbestos-induced occupational diseases]. / Diagnostik und Begutachtung asbestbedingter Berufskrankheiten.

Due to latency periods that can last for decades, asbestos-related diseases show 18 years after the enforcement of the prohibition of asbestos application in Germany their highest numbers. In the centre of attention are asbestos-induced pleural fibroses, mesotheliomas, asbestoses, lung and laryngeal cancer. Diagnosing and expertizing these diseases causes difficulties, is hitherto non-uniform and does frequently not correspond to the current medico-scientific expertise. This induced the German Respiratory Society as well as the German Society of Occupational and Environmental Medicine in cooperation with the German Society of Pathology, the German Radiology Society and the German Society of Otorhinolaryngology, Head and Cervical Surgery, to develop the above mentioned guideline during seven meetings moderated by AWMF. The required thorough diagnosis is based on the detailed recording of a qualified occupational history. Since the sole radiological and pathological-anatomical findings cannot sufficiently contribute to the causal relationship the occupational history recorded by a general physician and a specialist is of decisive importance. These physicians have to report suspected occupational diseases and to advise patients on social and medical questions. Frequently, problems occur if the recognition of an occupational disease is neglected due to a supposedly too low exposure or too few ferruginous bodies or low fibre concentrations in lung tissue. The new S2k directive summarizing the current medico-scientific knowledge is for this reason, for diagnoses and expert opinions as well as for the determination of a reduced capacity for work a very important source of information.

[Further development of the International Pneumoconiosis Classification--from ILO 1980 to ILO 2000 and to ILO 2000/German Federal Republic version]. / Die Weiterentwicklung der Internationalen Staublungenklassifikation - von der ILO 1980 zur ILO 2000 und zur ILO 2000/Version Bundesrepublik Deutschland.

The ILO (1980) Classification has been revised during recent years. The new version is now available as the International Classification of Radiographs of Pneumoconioses (Revised edition 2000). The Guidelines booklet is currently available only in English. Those involved felt it was important to maintain continuity with the ILO (1980) edition, in particular to retain the standard radiographs, despite their restricted quality, so as to ensure comparability with earlier national and international data sets. The standard films illustrating pleural abnormalities, and 'u'-shadows, have been modified and reconstituted. The most important changes relate to assessment of film quality, pleural abnormalities, and additional symbols. In Germany, film quality is characterised as "+", "+-", "+--" and "u" according to whether the ability to assess pneumoconiosis is judged to be unimpeachable ("+") to unusable ("u"). If a film is not classified as "+", then written comments regarding defects are required. For "diffuse" pleural thickening, the ILO (2000) edition now requires the presence also of obliteration of the costophrenic angle. This was not required in the earlier (1980) edition and, as previously, is also not stipulated in the German version. A minimum width of 3 mm (previously 0-5 mm), coded "a", is required both for plaques as well as for the margin to the lateral chest wall. Congruence is thus achieved for criteria, which, in German practice, lead to an indication of suspect occupational disease. Plaques on the diaphragm are not considered for measurement of extent; they are only coded as present or absent. If calcification is identified, then this must also be classified and measured as a localised plaque. Extent of calcification on its own, previously coded "0" to "3", is no longer specified. The following new symbols, illustrated by new diagrams, have been introduced: aa = atherosclerotic aorta; at = apical thickening; cg = calcified granuloma (or other non-pneumocononiotic nodules); me = mesothelioma (already previously differentiated from "ca" on the German record sheet); pa = plate atelectasis; pb= parenchymal bands; ra = rounded atelectasis; od = other disease. (Examples of the latter are illustrated diagrammatically by lobar pneumonia, aspergilloma, goiter and hiatal hernia.) Earlier national differences (ILO 1980/German Federal Republic) on particular issues have also been agreed among German "double-readers" ["Zweitbeurteiler"]. However, conformity between the original (ILO 2000) text and the national (German) modified text has been retained in large measure. The detailed descriptions of the standard films differ in certain respects from the German (1980) definitions. Some revision of individual descriptions of the films are proposed. Except for a few differences, agreement was reached here too. The definitive date for the change in Germany is expected to be in early 2004. The standard films are already available now through ILO offices in Geneva or Bonn (addresses in appendix.)

[Interstitial pulmonary siderofibrosis: requirements for acceptance as new occupational disease]. / Schweisserlungenfibrose: Begründung für die Aufnahme als neue Berufskrankheit.

BACKGROUND: Pulmonary siderosis is a well established disorder in welders. Internationally more than 150 cases of interstitial pulmonary siderofibrosis are associated with long-standing and heavy exposure to welding fumes at poorly ventilated working places. PATIENTS: Characteristic job histories, lung function analyses and histological examinations as well as elemental microanalysis by energy dispersive X-ray analysis (EDX) are demonstrated from 3 welders with pulmonary siderofibrosis. RESULTS: Histological examinations show a patchy interstitial fibrosis with accumulations of particulate material typical for welding fumes. EDX disclose an increase of iron-load in activated macrophages as well as in lung tissue and a close topographical relationship of welding fume particles and interstitial fibrotic reactions. Lung function analysis showed predominantly loss of pulmonary performance during spiroergometry. CONCLUSIONS: Regarding the actual knowledge about the pathomechanisms of ultrafine particles on lung tissue, the evidence from animal experiments, the histological and electron microscopical results, our own clinical examinations of welders and some epidemiological evidence, we assume a causal relationship of interstitial pulmonary siderofibrosis in welders with long-standing exposure to high concentrations of welding fumes under poor working conditions.

Interstitial pulmonary fibrosis after severe exposure to welding fumes.

BACKGROUND: Interstitial pulmonary fibrosis (IPF) is reported after long term, severe exposure to welding fumes in poorly ventilated workplaces. METHODS: Fifteen welders with IPF were examined--13 in our outpatient clinic--from 1990 to 1997. Occupational histories and examinations, lung function analyses, symptoms and clinical findings, histological analyses in 13 patients partly including SEM/EDX-analyses, chest X-rays, chest computed tomographies were conducted. RESULTS: Duration of work as welders was 28 years and the cumulative dose of welding fumes 221 mg/m(3) x years (median). Lung function studies found pattern of restriction or combined restriction-obstruction, lower diffusion capacity, and reduced blood oxygen tension at exercise. Histologically, patchy interstitial fibrosis was noted. Accumulations of particulate matter typically for welding fume were detected. EDX showed increase of iron load and close topographical relationship to welding fume particles embedded in areas of scattered fibrosis. CONCLUSION: While epidemiological data are limited, it is reasonable to conclude that a causal relationship exists between IPF in welders with long term exposure to high concentrations of welding fumes.

Inorganic fibres in the lung tissue of Hungarian and German lung cancer patients.

OBJECTIVE: To ascertain the lung burden of asbestos fibres in Hungarian lung cancer patients in comparison with the cumulative asbestos exposure estimated from the occupational history. METHODS: For 25 Hungarian lung cancer patients, lung tissue fibre analysis was performed by scanning transmission electron microscopy (STEM) and counting of ferruginous bodies (FBs) by light microscopy. Cumulative asbestos exposure in fibre-years was assessed from a standardised occupational history using the report "fibre years" of the German Berufsgenossenschaften. RESULTS: Median and maximum concentrations of fibres longer 5 microns per gram dry lung tissue (g dry) were 0.03 and 7.38 million fibres/g dry for chrysotile, 0.00 and 0.21 million fibres/g dry for amphibole and 0.22 and 0.62 million fibres/g dry for other mineral fibres (OMFs). The maximum values were observed in one patient for whom a high asbestos exposure was evident in advance from the occupational history. CONCLUSIONS: In comparison with reference values obtained by the same method for German patients with no indication of workplace asbestos exposure, increased concentrations of more than 0.2 million chrysotile fibres/g dry were obtained for six of the 25 Hungarian patients (24%). For one of them, the second highest estimate of a workplace exposure of 60 fibre-years and the highest tissue concentration of 7.38 million chrysotile fibres/g dry substantiate a high probability of a causal relationship to asbestos. A further comparison can be made with the results for 66 German patients treated by surgical lung resection for a disorder other than mesothelioma, mainly lung cancer. For the Hungarian lung cancer patients, similar amounts of chrysotile but distinctly lower amounts of amphibole fibres and distinctly higher amounts of OMFs were observed. A correlation between exposure estimates from occupational history and concentration of fibres in the lung tissue was observed for amphibole (Spearman: R = 0.66, P < 0.001, Pearson: R = 0.50, P = 0.01) and for chrysotile (Pearson: R = 0.48, P = 0.02).

[Asbestos-induced malignant mesothelioma of the tunica vaginalis testis]. / Asbestverursachtes malignes Mesotheliom der Tunica vaginalis testis.

Since 1977 the diffuse malignant mesothelioma of the pleura and peritoneum caused by asbestos represents one of the most often compensated occupational cancers in Germany. Because of the probability of an asbestos-related etiology, it is considered as a "signal tumour", mainly indicating exposure to asbestos dust at the workplace. Two cases of histologically confirmed rare malignant mesothelioma of the tunica vaginalis testis are presented. Previous exposure to asbestos at the workplace is to be considered as a causal factor in both tumors. If cases of mesothelioma occur the criteria for indicating an occupational disease (No. 4105 of the German Law of Occupational Diseases, BKV) are fulfilled.

Asbestos and man-made vitreous fibers as risk factors for diffuse malignant mesothelioma: results from a German hospital-based case-control study.

BACKGROUND: This study examines the role of occupational factors in the development of diffuse malignant mesothelioma with special emphasis on the dose-response relationship for asbestos and on the exposure to man-made vitreous fibers (MMVFs). METHODS: One hundred and twenty-five male cases, diagnosed by a panel of pathologists, were personally interviewed concerning their occupational and smoking history. The same number of population controls (matched for sex, age and region of residence) underwent similar interviews by trained interviewers. Odds ratios (OR) were calculated for an expert-based exposure index using conditional logistic regression. RESULTS: Exposure to asbestos shows the expected sharp gradient with an OR of about 45 for a cumulative exposure > 1.5 fiber years (arithmetic mean 16 fiber years). A significant OR was calculated even for the lowest exposure category "> 0 - < or = 0.15 fiber years". Although the mean cumulative exposure to MMVF is roughly 10% of the exposure to asbestos, an increased OR is observed in an ever/never evaluation. This observation is heavily hampered by methodical problems. A corresponding case-control study was performed using a lung tissue fiber analysis in addition to interviews. Both interviews and the lung tissue analysis yielded similar OR levels between the reference and the maximum exposure intervals. CONCLUSIONS: Despite a possible influence as a result of selection and information bias, our results confirm the previously reported observation of a distinct dose-response relationship even at levels of cumulative exposure below 1 fiber year. Moreover, the study confirms that asbestos is a relevant confounder for MMVF. A causal relationship between exposure to MMVF and mesothelioma could neither be detected nor excluded, as in other studies.

Pleural mesothelioma associated with indoor pollution of asbestos.

This case report concerns a 46-year-old woman, dying from histologically confirmed diffuse malignant mesothelioma after asbestos exposure, which was only caused by indoor pollution from crocidolite-containing spray asbestos in building materials. There was no other known occupational or environmental asbestos exposure during her life. The lung tissue fibre analysis by light microscopy showed significantly increased concentrations of ferruginous bodies (3162 FB per gram of wet lung tissue). By use of scanning transmission electron microscopy, clearly increased concentrations of amphibole fibres (8.6 x 10(6) fibres longer than 1 microm and 0.6 x 10(6) fibres longer than > or =5 microm per gram dry tissue), mainly classified as crocidolite, were observed. The disease was attributed to indoor exposure to sprayed asbestos, which occurred during her work as a decorator in the studio of a warehouse.

Human toxicokinetics of inhaled monochlorobenzene: latest experimental findings regarding re-evaluation of the biological tolerance value.

OBJECTIVE: The aim of this study was to obtain toxicokinetic data on the absorption and elimination of monochlorobenzene (MCB) in blood and its main metabolite 4-chlorocatechol (4-ClCat) as well as on the isomeric chlorophenols (o-ClPh, m-ClPh, and especially p-CIPh as the main ClPh metabolite) in urine for reevaluation of the biological tolerance (BAT) value of MCB. METHODS: Eight subjects performed 8-h inhalation tests daily over five successive days in an exposure chamber, at a maximum allowable concentration at the workplace (MAK) value of 10 ppm MCB. Five and two probands carried out the test series during physical activity levels of 75 and 50 W, respectively, for 10 min/h on a bicycle ergometer, and one subject was exposed continuously while at rest. MCB and its metabolites were analyzed by gas chromatography in combination with mass spectrometry. RESULTS: The mean MCB blood concentration of the five subjects exposed during physical activity of 75 W was 217 +/- 42 microg/l. The relationship of the mean blood concentration measured under the conditions of rest or 50 and 75 W activity levels was in a ratio of about 1:1.7:2.8. The half-life values in the first hour after ending the exposures were 53 min and 150 min for the ensuing period, with steady-state being reached after 45 min. The mean 4-ClCat concentration in urine at the end of the five days was 150 +/- 13 mg/g creatinine in the case of the subjects exposed at 75 W, which decreased to 25 mg/g creatinine at the beginning of the next exposure. The analogous p-ClPh concentrations were 25 +/- 2 and 9 +/- 2 mg/g creatinine. The elimination half-life values of the ClPh isomers ranged from 12.4 to 16.5 h, and the half-life of 4-ClCat was 6.4 h. There was no apparent tendency for MCB and its metabolites to accumulate in blood or urine. CONCLUSIONS: The results are in accordance with relevant field and laboratory studies. Taken into consideration with the 95th percentile, the evaluated BAT values should be set at levels of 300 microg MCB/l blood, 175 mg 4-ClCat/g creatinine or alternatively at 30 mg p-ClPh/g creatinine in urine after the end of a shift. At the beginning of the next shift, the BAT values of the metabolites should be 35 and 15 mg/g creatinine, respectively.

Role of occupational asbestos exposure in Hungarian lung cancer patients.

OBJECTIVE: What is the frequency of occupational asbestos exposure among patients suffering from malignant respiratory tumours and how many of these tumours are associated with asbestos in Hungary? METHODS: An internationally established questionnaire with 29 questions, covering the most characteristic activities of asbestos exposure at the workplace was completed for 300 patients with respiratory malignancies, i.e. 297 patients with lung cancer and three with mesothelioma of the pleura. From the questionnaire, the smoking habits were estimated and cumulative asbestos exposure was assessed in fibre-years. Additionally, lung X-rays were classified and the national data on the incidence of malignant pleura mesothelioma were analysed. RESULTS: A cumulative asbestos exposure of 25 fibre-years or more was detected in 11 patients with lung cancer (4%) and in each of the three patients with pleural mesothelioma (100%). In a further 72 patients (24%), cumulative occupational asbestos exposure was assessed as below 25 fibre-years (between 0.01 and 23.9 fibre-years). In this group, car and truck mechanics, and installation and construction workers using asbestos-cement were registered. Among patients with an asbestos exposure of 25 fibre-years or more, six asbestos-cement production workers were observed, among them the three mesothelioma cases. A weak but significant association between positive X-ray findings and exposure estimates could be demonstrated. Additionally, results of the lung tissue fibre counts by scanning transmission electron microscopy were available for 25 of the lung cancer patients. A good correlation was observed between the asbestos fibre counts and the assessment of cumulative asbestos exposure. In Hungary, 84 cases of pleural mesothelioma were registered in 1997 and 73 in 1998. These numbers correspond to an annual incidence of about one new case per 100,000 inhabitants older than 15 years. CONCLUSIONS: The annual incidence of lung cancer in Hungary is about 6,000. Since in our series of lung cancer patients about 4% were observed, which could be accepted as representing occupational disease because of a cumulative exposure to 25 fibre-years or more, the annual asbestos related lung tumour incidences may be estimated to be approximately 150 or more. The proportion of nearly two estimated cases of lung cancer per case of pleural mesothelioma corresponds to international experience. Up to now, lung cancer cases only exceptionally have been registered as occupational diseases, i.e. they were seriously under-diagnosed in Hungary. For improving this situation, diagnostic assistance by a self-interview with a questionnaire covering the working history for all newly diagnosed lung cancer patients would be helpful.

Serum ras (p21) as a marker for occupationally derived lung cancer?

Certain subsets of the population are especially sensitive to carcinogens, and this can be determined using molecular biological methods. In the literature there has been evidence presented for the use of p21ras (ras) as a tumor marker for human carcinogenic substances such as asbestos, polycyclic aromatic hydrocarbons, and vinyl chloride in the workplace. In this study we have examined whether serum ras could serve as a biomarker for the early detection of occupationally derived lung cancer, with an emphasis on Schneeberger (radon-induced) lung cancer. Sera were taken from 65 male tumor patients. Fifty-nine patients suffered from primary lung cancer (including 18 patients with Schneeberger lung cancer and 12 patients with asbestos-related lung cancer). Additionally, 29 patients with non-malignant lung disease, and a healthy control group (44) including 32 former uranium miners of SDAG Wismut exposed to ionizing radiation (radon and its decay products) were examined. Ras protein was determined via three different methods: 1) immunoprecipitation followed by SDS-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blotting; 2) SDS-PAGE using 5-17% gradient gels followed by Western blotting; 3) pre-incubation with Blue Sepharose, SDS-PAGE on 5-17% gradient gels, and Western blotting. The results show that 1 ng ras protein was measurable in serum standards. This protein could not be detected in patient sera or in sera from any of the study groups. Thus, ras cannot be considered useful as a marker for the early detection of asbestos-induced or Schneeberger lung cancer.

Biological monitoring of standardized exposure to ethylbenzene: evaluation of a biological tolerance (BAT) value.

The results of standardized 8 h lasting exposures of n = 18 volunteers to ethylbenzene (EthBz) at levels of 25 and 100% of the maximum allowable concentrations at the workplace (MAK) value of 100 ppm as well as the results of field studies are considered to evaluate a biological tolerance (BAT) value for EthBz. On the basis of the relationship between the external and internal exposure a BAT value of 1.5 mg/l has been set for the EthBz concentration in blood as the most sensitive and specific parameter of exposure to this aromatic hydrocarbon. The interpretation of EthBz blood values has to take into account the short half-life of t1/2 = 0.5 +/- 0.08 h in the first hour after the end of exposure in which this aromatic hydrocarbon is eliminated from the blood. The additional determination of the EthBz metabolites mandelic acid (MA) and phenylglyoxylic acid (PGA), respectively, excreted in post shift urine as well as in urine samples at the beginning of the next shift shows good correlations with the external exposure. The biological half-life of MA was calculated to t1/2 = 5.3 +/- 1.1 h. Because the time of sampling can vary the relationship between the levels of MA to PGA the total concentration of the excreted metabolites depends less on this influence and is therefore better suited for monitoring exposed persons. On the basis of the standardized experiments a BAT value has been proposed of 2 g MA plus PGA corrected per gram creatinine. Both BAT values are adjusted to data which result from earlier standardized exposures during 30 min to EthBz under physical activity of 50 watt on a bicycle ergometer.

Biomarkers of genetic damage and inflammation in blood and bronchoalveolar lavage fluid among former German uranium miners: a pilot study.

Former East German uranium miners who are known to have been exposed to radon are estimated to be at high risk for lung carcinogenesis. Among these miners over 200 occupationally caused lung cancer cases are expected to occur each year, resulting in a total of 7,000-24,000 excess lung cancer cases in the coming years. It is still unknown whether there is a correlation between biomarkers and the exposure of the uranium miners to ionizing radiation that might enable us to trace those miners with high lung cancer risk. The primary aim of this pilot study was to test the possibility of performing a biomarker study in this unique cohort of former uranium miners in spite of several limitations that had to be taken into consideration when comparing them with healthy controls, such as old age, age-dependent diseases and potential confounding artefacts from dissimilar smoking patterns. The second aim was to test a range of biomarkers for DNA damage and inflammation in leukocytes and bronchoalveolar fluid for their ability to detect biological effects. In this cohort of miners we found an increased frequency of chromosomal aberrations in blood lymphocytes and an increased prevalence of both fibronectin and tumour necrosis factor alpha in the bronchoalveolar fluid.

Serum levels of pantropic p53 protein and EGF-receptor, and detection of anti-p53 antibodies in former uranium miners (SDAG Wismut).

BACKGROUND: The oncogene product EGF-receptor (EGF-R), the tumor suppressor gene product p53, and anti-p53 antibodies are detectable in serum of certain cancer patients. Increased levels of some of these products were reported in lung cancer patients after occupational asbestos exposure, after exposure to polycyclic aromatic hydrocarbons or vinyl chloride. This molecular epidemiological study investigated the use of serum EGF-R, p53-protein, and anti-p53 antibodies as biomarkers for detection of effects of radon and its decay products. METHODS: Serum EGF-R, p53-protein, and anti-53 antibodies were measured using ELISA in former uranium miners of SDAG Wismut without lung disease (n=106) and miners with Schneeberg lung cancer (n=22). They were compared with healthy subjects (n=23), patients with lung cancer not due to ionizing radiation (n=88), and patients with non-malignant lung or pleural diseases (n=50). RESULTS: No significantly elevated or decreased serum values for p53 protein, EGF-R, or anti-p53 antibodies could be found. There was no correlation of these with Working Level Months (WLM). CONCLUSIONS: p53 protein, EGF-R, or anti-p53 antibodies in serum are not useful as biomarkers for detection of lung cancer related to ionizing radiation (i.e., Schneeberg lung cancer).

p53 protein, EGF receptor, and anti-p53 antibodies in serum from patients with occupationally derived lung cancer.

The oncogene product epidermal growth factor receptor (EGF-R), the tumour suppressor gene product p53 and anti-p53 antibodies are detectable in the serum of certain cancer patients. Increased levels of some of these products were reported in lung cancer patients after occupational asbestos exposure and after exposure to polycyclic aromatic hydrocarbons or vinylchloride. In the first step, this study investigated the possible diagnostic value of serum EGF-R, p53-protein and anti-p53 antibodies, measured by an enzyme-linked immunosorbent assay, in lung tumour patients. In addition to being investigated on a molecular epidemiological basis, these parameters were examined as biomarkers of carcinogenesis, especially with regard to asbestos incorporation effects or of radon-induced lung cancers. Also, a possible effect of cigarette smoking and age dependence were studied. A total of 116 male patients with lung or pleural tumours were examined. The histological classification was four small-cell cancers, six large-cell cancers, 32 adenocarcinomas, 47 squamous carcinomas, 12 mixed lung carcinomas, five diffuse malignant mesotheliomas and ten lung metastasis of extrapulmonary tumours. Twenty-two lung cancers and all mesotheliomas were related to asbestos, 22 lung cancers were related to ionizing radiation and 61 patients had cigarette smoke-related lung cancer. Besides these patients 50 male patients with non-malignant lung or pleural diseases were included; of the latter eight subjects suffered from asbestosis. Controls were 129 male subjects without any lung disease. No significantly elevated or decreased serum values for p53 protein, EGF-R, or anti-p53 antibodies as a function of histological tumour type, age, or degree and type of exposure (asbestos, smoking, ionizing radiation) could be found. The utility of p53-protein, EGF-R and anti-p53 antibodies as routine biomarkers for screening occupationally derived lung cancers is limited.

Dose-response relationship between amphibole fiber lung burden and mesothelioma.

In a mesothelioma case-control study, asbestos and other mineral fibers from lung burden were examined as causal factors. Diagnosis was confirmed by a panel of pathologists. For 66 cases and 66 controls from hospitals in five German towns, lung tissue fiber analysis by transmission electron microscopy was available. Control patients were treated by a surgical lung resection mostly because of lung cancer. For chrysotile and other mineral fibers a significantly increased odds ratio (OR) was not observed. A clear dose-response relationship was demonstrated for the concentration CA of amphibole fibers longer than 5 microm. Between 0.025 and 2.5 fibers/microg dry weight (f/microg) the relationship can be approximated as OR = CA/(0. 025 f/microg). Similar but less distinct dose-response relationships were found in a Canadian and an Australian study. It is concluded that among German mesothelioma patients factors not associated with amphibole fiber concentration are not predominating.