Nieuwsarchief

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. jaap.keijer@wur.nl

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

De vraag of longkanker door asbest is veroorzaakt terwijl er geen sprake is van asbestose, blijft controversieel. Dit concluderen Engelse onderzoekers na analyse van 9 epidemiologische artikelen. De momenteel beschikbare technische middelen bieden niet voldoende mogelijkheden om dit te onderzoeken. Waarschijnlijk is het type asbestvezel van belang, concluderen Engelse en Amerikaanse onderzoekers.

Bron: Thorax. vol. 60 (2005), afl. 5, pag. 433-436 (4)

Asbestos, asbestosis, and lung cancer : a critical assessment of the epidemiological evidence

Hessel, P.A.. Gamble, J.F.. Mcdonald, J.C. / In: Thorax. vol. 60 (2005), afl. 5, pag. 433-436 (4)

The question of whether lung cancer can be attributed to asbestos exposure in the absence of asbestosis remains controversial. Nine key epidemiological papers are reviewed in a point/counterpoint format, giving the main strengths and limitations of the evidence presented. Of the nine papers, two concluded that asbestosis was necessary and seven that it was not. However, the study design, nature and circumstances of exposure and method of analysis of the studies differed considerably, and none was considered definitive. It is concluded that, because of the relative insensitivity of chest radiography and the uncertain specificity of findings from histological examinations or computed tomography, it is unlikely that epidemiology alone can put either the strict scientific or practical medicolegal questions beyond doubt. It is probable that the issue may depend critically on asbestos fibre type, an aspect not so far addressed.

In Woodstock werd in 1985 asbestvervuiling ontdekt in het drinkwater. Dit kwam door asbestcementpijpen die half jaren 50 waren geïnstalleerd. De kankerstatistieken van Woodstock werden over de periode 1980-1998 vergeleken met nationale gegevens. Er werd geen relatie met asbest gevonden.

Bron: Browne, M. L. et al. (2005). Environmental research. vol. 98 (2005), afl. 2, pag. 224-232 (9)

Cancer incidence and asbestos in drinking water, Town of Woodstock, New York, 1980#x0201.1998

Browne, Marilyn L.. Varadarajulu, Deepa. Lewis-Michl, Elizabeth L.. Fitzgerald, Edward F. / In: Environmental research. vol. 98 (2005), afl. 2, pag. 224-232 (9) / 2005

Abstract

Late in 1985, asbestos contamination was discovered in the public water supply of the Town of Woodstock, Ulster County, New York. Contamination resulted from asbestos’cement pipes installed in the town water system in the mid to late 1950s and the corrosiveness of the local water. The New York State (NYS) Department of Health established the Woodstock Asbestos Exposure Registry (WAER) in 1986 to monitor rates of cancer among individuals who lived on the water supply between 1960 and 1985. Demographic, health, and residential information were collected on 2936 registrants. The follow-up period for observation of cancer was 1980-1998, consistent with the expected lag of 20-30+ years for development of asbestos-related cancers. The NYS Cancer Registry was used to ascertain cancer diagnoses. Standardized incidence ratios (SIRs) for gastrointestinal, respiratory, and total cancers were all approximately 1.00 or less and all 95% confidence intervals (CIs) included 1.00. For individual types of the gastrointestinal cancers, only the SIR for pancreatic cancer was marginally statistically significant at 2.19 (95% CI=1.00-4.16), based on a total of nine observed cases. The excess in pancreatic cancer occurred primarily among men (SIR=3.08. 95% CI=1.13-6.70) and was only slightly elevated among women (SIR=1.39. 95% CI=0.29-4.06). This association may be related to factors other than asbestos exposure such as occupation and lifestyle or to chance. No cases of mesothelioma were observed among WAER participants. There was no increase in incidence by latency or duration of residence on the water supply, but the ability to detect these trends is limited by small numbers and unknown dates of initial exposure. The general pattern of results did not demonstrate a likely link between exposure to asbestos in drinking water and cancer occurrence among participants in the WAER.

Alpha-TOS, een soort vitamine E, heeft in experimenten met muizen mesothelioomkankercellen gedood en de groei van tumoren tegengehouden, zegt de Australische celbioloog Dr. Neuzil. Hij hoopt dat het middel over ongeveer 2 jaar bij mensen kan worden getest.

Bron: The Courier Mail, Daily Telegraph, 23 mei 2005.

The Courier Mail (Queensland, Australia)

May 23, 2005 Monday

HEADLINE: Vitamin cancer treatment hope

BODY:

A VITAMIN E-related compound may kill deadly cancer cells caused by asbestos exposure, says an Australian cell biologist who has already established its success in trials using mice.

Gold Coast-based Griffith University researcher Jiri Neuzil said alpha-TOS, which is closely related to vitamin E, killed mesothelioma cancer cells in experiments with mice.

Most victims of mesothelioma, an aggressive cancer that destroys a protective membrane covering internal organs including the lungs, have inhaled asbestos particles.

Dr Neuzil said alpha-TOS also halted growth of mesothelioma tumours, for which there is currently no cure, under a five-year study involving researchers from Australia, Italy and the Czech Republic.

He said the compound had also showed hints of suppressing breast cancer, melanoma, lung cancer and colon cancer tumours in animal experiments. Dr Neuzil said alpha-TOS would ultimately be put to the test in human trials, which he hoped to begin within two years.

Alpha-TOS was selective because it pursued mesothelioma cancer cells but caused only minor damage, if any, to normal cells in mice, he said.

Dr Neuzil said he stumbled on the compound’s promising qualities “by mistake five years ago.