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In het Amerikaanse CARET onderzoek werden 4060 beroepsmatig aan asbest blootgestelde mannen en 14.254 zware rokers gedurende 10 tot 18 jaar gevolgd. De onderzoekers vonden een relatief hoog risico op dikke darmkanker bij de subgroep zware rokers die aan asbest was blootgesteld geweest en bij wie op röntgenfoto’s van het longvlies niet-kwaadaardige abestgerelateerde afwijkingen waren te zien. Bron: Aliyu OA. et al. (2005). Evidence for Excess Colorectal Cancer Incidence among Asbestos-exposed Men in the Beta-Carotene and Retinol Efficacy Trial. Am J Epidemiol. Nov 1.162(9):868-78.

Aliyu OA, Cullen MR, Barnett MJ, Balmes JR, Cartmel B, Redlich CA, Brodkin CA, Barnhart S, Rosenstock L, Israel L, Goodman GE, Thornquist MD, Omenn GS.

Abstract

The relation between asbestos exposure and colorectal cancer remains controversial. The authors of this 1984-2004 US study examined the association among 3,897 occupationally exposed participants in the Beta-Carotene and Retinol Efficacy Trial (CARET) for chemoprevention of lung cancer, followed prospectively for 10-18 years. When a Cox stratified proportional hazards model was used, risks of colorectal cancer were elevated among male heavy smokers exposed to asbestos. Their relative risk was 1.36 (95% confidence interval: 0.96, 1.93) when compared with that for CARET heavy smokers not exposed to asbestos, after adjusting for age, smoking history, and intervention arm. The presence of asbestos-induced pleural plaques at baseline was associated with a relative risk of 1.54 (95% confidence interval: 0.99, 2.40). colorectal cancer risk also increased with worsening pulmonary asbestosis (p = 0.03 for trend). A dose-response trend based on years of asbestos exposure was less evident. Nonetheless, these data suggest that colorectal cancer risk is elevated among men occupationally exposed to asbestos, especially those with evidence of nonmalignant asbestos-associated radiographic changes.

“Soluble mesothelin-related protein”(SMRP) is een proteïne die in het bloedplasma voorkomt. In dit onderzoek werden 48 mesothelioompatiënten vergeleken met een controlegroep van 228 mensen, gezond of met een andere ziekte deels wel, deels niet aan asbest blootgesteld. De resultaten ondersteunen de hypothese dat SMRP behulpzaam kan zijn bij de diagnose van maligne mesothelioom, bij de beoordeling van de ziekte-progressie en bij de vroeg-screening van deze ziekte. Bron: Robinson BW, et al. (2005). Soluble mesothelin-related protein:a blood test for mesothelioma. Lung Cancer. 2005 Jul.49 Suppl 1:S109-11.

Robinson BW, Creaney J, Lake R, Nowak A, Musk AW, de Klerk N, Winzell P,

Abstract

Identification of tumor marker for mesothelioma (MM) might prove useful in

diagnosis as well as for monitoring tumor in response to therapy and for

screening at-risk individuals. We tested the hypothesis that soluble

mesothelin-related protein (SMRP), a mesothelin family member, in the serum

would be such a marker. Our data show that determination of SMRP in serum is a

marker of MM with a sensitivity of sensitivity 83% and specificity 95% in the

first 48 MM patients tested. Changes in serum SMRP levels parallel clinical

course/tumor size and SMRP is elevated in 75% of patients at diagnosis. SMRP

should also be useful for monitoring disease progression, and importantly, may

prove useful for screening asbestos-exposed individuals for early MM.

Bhattacharya en collega’s beschrijven in dit overzichtsartikel het totaal aan biologische reacties in het lichaam nadat iemand aan asbest is blootgesteld. Onderscheid wordt gemaakt naar indicatoren van (1) blootstelling (reacties op vezels), (2) effect (ziekte) en (3)kwetsbaarheid (verschillen tussen individuen en/of populaties). Bron: Bhattacharya K, Dopp E, Kakkar P, Jaffery FN, Schiffmann D, Jaurand MC, Rahman I, Rahman Q. (2005). Biomarkers in risk assessment of asbestos exposure. Mutation Research, Aug 17, article in press.
Bhattacharya K, Dopp E, Kakkar P, Jaffery FN, Schiffmann D, Jaurand MC, Rahman I, Rahman Q. (2005). Biomarkers in risk assessment of asbestos exposure. Mutation Research, Aug 17, article in press. 9: Mutat Res. 2005 Aug 17. [Epub ahead of print]

Abstract

Developments in the field of molecular epidemiology and toxicology have given

valuable tools for early detection of impending disease or toxic condition.

Morbidity due to respiratory distress, which may be due to environmental and

occupational exposure, has drawn attention of researchers worldwide. Among the

occupational exposure to respiratory distress factors, fibers and particles have

been found to be main culprits in causing diseases like asbestosis, pleural

plaques, mesotheliomas and bronchogenic carcinomas. An early detection of the

magnitude of exposure or its’ effect using molecular end points is of growing

importance. The early inflammatory responses like release of the inflammatory

cells collected by non-invasive methods give an indication of the unwanted

exposure and susceptibility to further complications. Since free radicals like

O(2)(-), OH, OOH, NO, NOO, etc. are involved in the progression of

asbestos-related diseases and lead to cytogenetic changes, an evaluation of

antioxidant states reducing equivalents like GSH and ROS generation can be a

good biomarker. The cytogenetic end points like chromosomal aberration,

micronucleus formation and sister chromatid exchange give indication of genetic

damage, hence they are used as effective biomarkers. New techniques like

fluorimetric analysis of DNA unwinding, alkaline elution test, fluorescent in

situ hybridization and comet assay are powerful tools for early detection of

initiation of disease process and may help in planning strategies for minimizing

morbidity related to asbestos fiber exposure. The present review article covers

in detail possible biomarkers for risk assessment of morbidity due to

fibers/particles in exposed population.

Bêtacaroteen is een stof die in het lichaam wordt omgezet in vitamine A, een zgn. provitamine. Het komt voor in fruit en groenten. In dit overzichtsartikel wordt aan de hand van genetische technieken nagegaan hoe deze stof werkt in het lichaam. Bêtacaroteen lijkt namelijk zowel positieve als negatieve effecten voor de gezondheid te kunnen hebben. Enerzijds werkt het, bij normale inname, als antioxidant en beperkt daarmee o.a. het risico op kanker. Anderzijds is bij inname van extra doses, buiten de normale voeding, een verhoogd risico op longkanker waargenomen bij zware rokers en mensen die met asbest hebben gewerkt. Hoewel hiervoor verschillende verklaringen te geven zijn, concluderen Keijer en collega’s dat nog niet duidelijk is hoe bêtacaroteen deze effecten kan veroorzaken.

Bron: Keijer, J. et al. (2005). Beta-carotene and the application of transcriptomics in risk-benefit evaluation of natural dietary components. Biochim Biophys Acta. May 30.1740(2):139-46.

Abstract

Keijer J, Bunschoten A, Palou A, Franssen-van Hal NL.

RIKILT-Institute of Food Safety, Food Bioactives Group. Bornsesteeg 45, P.O. Box

230, 6700 AE, Wageningen, The Netherlands. [email protected]

Beta-carotene is a natural food component that is present in fruits and

vegetables and is also used as a food colorant and a supplement. Beta-carotene

is an anti-oxidant and a source of vitamin A. It is endowed with health

beneficial properties, but a number of studies showed that with high intakes it

may increase the risk for lung cancer in at risk individuals (heavy smokers,

asbestos workers and alcohol users). To establish the window of benefit, it is

necessary to identify early markers of effect and to obtain insight in the

mechanism of action of beta-carotene, in the absence and presence of

environmental risk factors. Genomics technologies are well suited to dissect the

mechanisms of action and identify the markers of effect. Human cell lines can be

used to analyse the effects of beta-carotene, but exposure studies with

beta-carotene show that cell lines display a widely variant behaviour, which

hampers translation to the in vivo situation in humans. Alternatively, animal

studies can be used. Especially the ferret seems to be a good model, but little

sequence information of this species is available. However, heterologous

hybridization on human cDNA seems possible and provides and a new tool for

molecular analysis of health effects of beta-carotene.

In de Nelson screeningsstudie is 70% van de longkankers, met behulp van een multi-slice CT scan, in een zeer vroeg en goed behandelbaar stadium ontdekt. Dit resultaat bespraken de onderzoekers in een bijeenkomst op 7 oktober j.l. Vaak is longkanker op het moment dat het ontdekt wordt al uitgezaaid naar andere delen van het lichaam en daardoor in 80% van de gevallen niet meer te opereren. De nieuwe CT techniek zou een belangrijke rol in de bestrijding van longkanker kunnen gaan spelen. Het Nelson-onderzoek is het enige grootschalige proefbevolkingsonderzoek op longkanker in Europa. Het wetenschappelijke bevolkingsonderzoek is gestart in september 2003 onder mannen en vrouwen tussen 50 en 75 jaar in een aantal regio’s. 16.000 Personen met een verhoogd risico op longkanker doen mee aan het onderzoek. De Gezondheidsraad schat dat iets meer dan 10% van de gevallen van longkanker gerelateerd is aan asbestblootstelling. Bron: Artsennet.nl, 10 oktober 2005.

Robinson en collega’s beschrijven de ontwikkelingen in de diagnostiek en behandeling van mesothelioom (longvlies-, buikvlieskanker) en het onderzoek naar de oorzaken. Zij bestudeerden artikelen geregistreerd in de medische databank Pubmed en webpagina’s naar aanleiding van een zoekopdracht in Google. Volgens de schrijvers is het inmiddels alom bekend in het westen dat asbest kanker kan veroorzaken en kennen steeds meer mensen het woord mesothelioom. Een aanwijzing hiervoor was een zoekopdracht naar deze term in Google die maar liefst 3 miljoen webpagina’s opleverde, meer dan voor meer bekende kankersoorten als bijvoorbeeld leukemie.

Bron: Robinson, B.W. et al. (2005). Malignant mesothelioma. The Lancet, vol 366, 30 juli, 397-408.

Robinson, B.W., Musk, A.W. & Lake, R.A. (2005). Lancet 2005.366:397 -408

Abstract

Malignant mesothelioma is an aggressive,treatment-resistant tumour,which is increasing in frequency throughout the world.Although the main risk factor is asbestos exposure,a virus,simian virus 40 (SV40),could have a role. Mesothelioma has an unusual molecular pathology with loss of tumour suppressor genes being the predominant pattern of lesions,especially the P 16 INK4A, and P 14ARF ,and NF 2 genes,rather than the more common p 53 and Rb tumour suppressor genes.Cytopathology of mesothelioma effusions or fine-needle aspirations are often sufficient to establish a diagnosis,but histopathology is also often required.Patients typically present with breathlessness and chest pain with pleural effusions.Median survival is now 12 months from diagnosis.Palliative chemotherapy is beneficial for mesothelioma patients with high performance status.The role of aggressive surgery remains controversial and growth factor receptor blockade is still unproven.Gene therapy and immunotherapy are used on an experimental basis only. Patterns identified from microarray studies could be useful for diagnosis as well as

prognostication.

Een cohort van 726 vuurtorenwachters dat in de periode vanaf 1917 tot 1967 werkzaam was geweest werd onderzocht op kankerincidentie in de periode 1960 tot 2002. Bij de subgroep die asbest via drinkwater had binnengekregen werd een relatief hoge incidentie van maag-darmkanker gevonden. Bron: Kjaerheim, K. et al. (2005).Cancer of the gastrointestinal tract and exposure to asbestos in drinking water among lighthouse keepers (Norway). Cancer causes and control. vol. 16 (2005), afl. 5, pag. 593-598 (6).

Kjaerheim, Kristina. Ulvestad, Bente. Martinsen, Jan Ivar. Andersen, Aage / In: Cancer causes and control. vol. 16 (2005), afl. 5, pag. 593-598 (6) / 2005

Abstract

Objective Previous studies of predominantly ecological design have indicated a possible elevation of gastrointestinal cancer risk in population groups exposed to drinking water contaminated with asbestos from natural sources or asbestos’ cement containing water pipes. In the present study the possible effect of ingested asbestos fibers on gastrointestinal cancer risk was investigated in an occupational group where a proportion of the employees was exposed to asbestos in their drinking water.

Method A cohort of 726 lighthouse keepers first employed between 1917 and 1967 were followed up for cancer incidence from 1960 to 2002. The standardized incidence ratio (SIR) was calculated as the number of new cancer cases divided by the expected number based on five-year age and sex specific incidence rates in the general rural population of Norway. A 95% confidence interval (CI) was calculated for all SIR values assuming a Poisson distribution of the cancer cases.

Results Risk of stomach cancer was elevated in the whole cohort (SIR: 1.6, CI: 1.0-2.3), in the subgroup with definite asbestos exposure (SIR: 2.5, CI: 0.9-5.5), and when the group was followed for 20&#8201.years and more after first possible exposure (SIR: 1.7, CI: 1.1-2.7). Less consistent results were found for colon cancer. SIR was 1.5 (CI: 0.9-2.2) overall, 0.8 (CI: 0.1-2.9) among the exposed, and 1.6 (CI: 1.0-2.5) twenty years and more after first possible exposure.

Conclusion The results support the hypothesis of an association between ingested asbestos and gastrointestinal cancer risk in general and stomach cancer risk specifically.

De Stanton Hypothese stelt dat lange dunne asbestvezels meer kankerverwekkend zijn dan korte dikke vezels. De Amerikaanse onderzoeker Suzuki en collega’s vinden in dit pathologische onderzoek andere aanwijzingen. Het bestudeerde long- en mesotheelweefsel van 168 mesothelioompatiënten bevatte voor slechts 2,3% vezels die aan de Stanton hypothese voldeden (langer of gelijk aan 8 &#956.m en dunner of gelijk aan 0.25 &#956.m). Ongeveer 90% van de gevonden vezels was kort en dun (korter of gelijk aan 5 &#956.m en dunner of gelijk aan 0.25 &#956.m) en vaak van het chryostiel type (wit asbest). Zij concluderen dat ook korte dunne asbestvezels lijken bij te dragen aan het ontstaan van maligne mesothelioom.

Bron: Suzuki, Y, et al. (2005). Short, thin asbestos fibers contribute to the development of human malignant mesothelioma : pathological evidence. International journal of hygiene and environmental health. vol. 208, afl. 3, pag. 201-210 (10).

Short, thin asbestos fibers contribute to the development of human malignant mesothelioma : pathological evidence

Abstract

Based on animal studies, long and thin asbestos fibers (8 &#956.m in length and 0.25 &#956.m in width) have been postulated to be strongly carcinogenic inducing pleural malignant mesothelioma, while shorter, thicker fibers have been postulated to pose a lesser risk (Stanton hypothesis). The objective of this study is to test the validity of the Stanton hypothesis through direct pathologic analysis of human mesothelioma tissue. Digested bulk tissue samples, or ashed 25 &#956.m thick sections, or both, were prepared from lung and mesothelial tissues taken from 168 cases of human malignant mesothelioma. In these tissues, 10,575 asbestos fibers (4820 in the lung and 5755 in mesothelial tissues (1259 in fibrotic serosa and 4496 in mesotheliomatous tissue)) were identified by high-resolution analytical electron microscopy. Dimensions of these asbestos fibers were measured in printed electron micrographs. Results were as follows: (1) long, thin asbestos fibers c onsistent with the Stanton hypothesis comprised only 2.3% of total fibers (247/10,575) in these tissues. (2) the majority (89.4%) of the fibers in the tissues examined were shorter than or equal to 5 &#956.m in length (9454 of 10,575), and generally (92.7%) smaller than or equal to 0.25 &#956.m in width (9808 of 10,575). (3) Among asbestos types detected in the lung and mesothelial tissues, chrysotile was the most common asbestos type to be categorized as short, thin asbestos fibers. (4) Compared with digestion technique of the bulk tissue, ashing technique of the tissue section was more effective to detect short, thin fibers. We conclude that contrary to the Stanton hypothesis, short, thin, asbestos fibers appear to contribute to the causation of human malignant mesothelioma. Such fibers were the predominant fiber type detected in lung and mesothelial tissues from human mesothelioma patients. These findings suggest that it is not prudent to take the position that short asbestos fibers convey little risk of disease.

De overlevingskansen van kankerpatiënten in Noord-Holland/Flevoland zijn sinds 1988 duidelijk gestegen.Bij sommige vormen van kanker is echter weinig verbetering opgetreden. Dit geldt bijvoorbeeld voor longkanker en mesothelioom (longvlies-/buikvlieskanker). Bron: IKCnet.nl, 1 augustus 2005. Meer http://www.ikcnet.nl/nieuws/index.php?id=1220

Nog steeds is niet helemaal duidelijk hoe asbest kanker veroorzaakt. Men denkt dat ijzer daarbij een rol speelt. De meest gevaarlijke asbestsoorten hebben een relatief hoog ijzergehalte. Baldys en Aust onderzochten de werking van asbestvezels en ijzer op de Epidermale Groei Factor Receptor (EGFR) in menselijke epitheel en mesotheelcellen uit long en longvlies. Zij gebruikten drie soorten asbest, t.w. crocidoliet, amosiet en chrysotiel met respectievelijk 27, 27 en 2% ijzer. Zij vonden dat ingekapselde crocidoliet asbestvezels de EGFR receptor inactiveerden en daarmee indirect de celdeling kunnen ontregelen. IJzer lijkt daarbij een mediërende werking te hebben. Baldys, A. & Aust, A.E. (2005). Role of Iron in Inactivation of Epidermal Growth Factor Receptor after Asbestos Treatment of Human Lung and Pleural Target Cells. American journal of respiratory cell and molecular biology. vol. 32, afl. 5, pag. 436-442 (7).
American Journal of Respiratory Cell and Molecular Biology. Vol. 32, pp. 436-442, 2005

Abstract

Although the mechanism by which asbestos causes cancer remains unknown, iron associated with asbestos is thought to play a role in the pathogenic effects of fibers. Here, we examined the effects of asbestos on the epidermal growth factor receptor (EGFR) in human lung epithelial (A549) cells, human pleural mesothelial (MET5A) cells, and normal human small airway epithelial (SAEC) cells. Treatment of A549, MET5A, and SAEC cells with asbestos caused a significant reduction of EGFR tyrosine phosphorylation. This was both time- (15 min to 24 h) and concentration-dependent (1.5, 3, and 6 µg/cm2) in A549 cells. Also, treatment with 6 µg/cm2 crocidolite for 24 h diminished the phosphorylation levels of human EGFR 2 (HER2). Exposure of A549 cells to 6 µg/cm2 crocidolite for 3–24 h resulted in no detectable Y1045 phosphorylation and no apparent degradation of the EGFR. Inhibition of fiber endocytosis resulted in a considerable inhibition of EGFR dephosphorylation. Removal of iron from asbestos by desferrioxamine B or phytic acid inhibited asbestos-induced decreases in EGFR phosphorylation. The effects of crocidolite, amosite, and chrysotile on the EGFR phosphorylation state appeared to be directly related to the amount of iron mobilized from these fibers. These results strongly suggest that iron plays an important role in asbestos-induced inactivation of EGFR.