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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

In de West-australische plaats Wittenoom werd van 1943 tot 1966 het gevaarlijke blauwe asbest gewonnen (crocidoliet). In 2002 werden 1885 inwoners, waarvan 1042 (ex-)werknemers onderzocht op asbestose (stoflongen) en bepaalde vitamine-niveaus in het bloed (retinol, caroteen en vitamine E). De onderzoekers vonden een relatie tussen chronisch lagere vitamine-niveaus en een grotere kans om aan asbestose te overlijden. Van de onderzoeksgroep overleden 76 personen aan asbestose, een te kleine groep om causaliteit te kunnen bepalen. Meer onderzoek is nodig.

Bron: Alfonso, H.S. et al. (2005). Plasma Concentrations of Retinol, Carotene, and Vitamin E and Mortality in Subjects With Asbestosis in a Cohort Exposed to Crocidolite in Wittenoom, Western Australia. Journal of occupational and environmental medicine. vol. 47, afl. 6, pag. 573-579 (7)

Alfonso, Helman S.. Fritschi, Lin. de Klerk, Nicholas H.. Ambrosini, Gina. Beilby, John. Olsen, Nola. Musk, A William (2005). Plasma Concentrations of Retinol, Carotene, and Vitamin E and Mortality in Subjects With Asbestosis in a Cohort Exposed to Crocidolite in Wittenoom, Western Australia. Journal of occupational and environmental medicine. vol. 47, afl. 6, pag. 573-579 (7).

Abstract

Objective:We sought to examine the relationships between plasma concentrations of retinol, carotene, and vitamin E and mortality associated with asbestosis in people previously exposed to crocidolite.

Methods:Cox regression modeling was applied to examine these relationships at the first measurement of each vitamin, at the measurement at each visit, and with the rate of change of each vitamin during the follow-up.

Results:There were 76 deaths of people with asbestosis during the follow-up period and 1885 subjects censored. Mortality in subjects with asbestosis was inversely related to plasma levels of retinol and Vitamin E concentrations and to their rate of increase during the follow-up. Carotene concentrations at first visit were associated with lower mortality but not during the follow up period.

Conclusions:Chronically low levels of these vitamins are associated with an increased risk of dying with asbestosis.

Asbest bestaat uit microscopisch kleine vezels. Er zijn verschillende soorten, onderverdeeld in serpentijnen en amfibolen. Serpentijnen hebben gekrulde vezels, de vezels van amfibolen hebben de vorm van staafjes en zijn gevaarlijker. Een groep ratten werd gedurende 5 dagen herhaaldelijk blootgesteld aan een groot aanta calidria chrysotiel vezels (serpentijn), een andere groep aan een aantal tremolietvezels (amfibool). Tot één jaar na de proef werd bij de ratten die aan chrysotiel waren blootgesteld geen ontstekingsreactie gezien. Dit in tegenstelling tot de aan tremoliet blootgestelde ratten die sterk reageerden, ondanks blootstelling aan 16 x minder vezels dan de aan chrysotiel blootgestelde ratten. Bernstein, D. et. al., (2005). Comparison of Calidria Chrysotile Asbestos to Pure Tremolite : Final Results of the Inhalation Biopersistence and Histopathology Examination Following Short-Term Exposure. Inhalation toxicology. vol. 17, afl. 9, pag. 427-450 (24).
Bernstein, David. Chevalier, Jörg. Smith, Paul (2005). Comparison of Calidria Chrysotile Asbestos to Pure Tremolite : Final Results of the Inhalation Biopersistence and Histopathology Examination Following Short-Term Exposure. Inhalation toxicology. vol. 17, afl. 9, pag. 427-450 (24).

Abstract:

Calidria chrysotile asbestos, which is a serpentine mineral, has been shown to be considerably less biopersistent than the durable amphibole mineral tremolite asbestos, which persists once deposited in the lung. The initial results of this inhalation biopersistence study in rats that demonstrates this difference were reported in Bernstein et al. (2003). This article presents the full results through 1 yr after cessation of the 5-day exposure. This study was based upon the recommendations of the European Commission (EC) Interim Protocol for the Inhalation Biopersistence of synthetic mineral fibers (Bernstein & Riego-Sintes, 1999). In addition, the histopathological response in the lung was evaluated following exposure. In order to quantify the dynamics and rate by which these fibers are removed from the lung, the biopersistence of a sample of commercial-grade chrysotile from the Coalinga mine in New Idria, CA, of the type Calidria RG144 and that of a long-fiber tremolite were studied. For synthetic vitreous fibers, the biopersistence of the fibers longer than 20 µm has been found to be directly related to their potential to cause disease. This study was designed to determine lung clearance (biopersistence) and the histopathological response. As the long fibers have been shown to have the greatest potential for pathogenicity, the aerosol generation technique was designed to maximize the number of long respirable fibers. The chrysotile samples were specifically chosen to have 200 fibers/cm 3 longer than 20 µm in length present in the exposure aerosol. These longer fibers were found to be largely composed of multiple shorter fibrils. The tremolite samples were chosen to have 100 fibers/cm 3 longer than 20 µm in length present in the exposure aerosol. Calidria chrysotile has been found to be one of the most rapidly cleared mineral fibers from the lung. The fibers longer than 20 µm in length are cleared with a half-time of 7 h. By 2 days postexposure all long fibers have dissolved/disintegrated into shorter pieces. The fibers between 5 and 20µm in length were cleared with a half-time of 7 days. This length range represents a transition zone between those fibers that can be fully phagocytosed and cleared as particles and the longer fibers that cannot be fully engulfed by the macrophage. The fibers/objects shorter than 5 µm in length were cleared with a half-time of 64 days, which is faster than that reported for insoluble nuisance dusts such as TiO 2 . By 12 months postexposure, 99.92% of all the remaining chrysotile was less than 5 µm in length. Following the 5 days of repeated exposure to more than 48,000 chrysotile fibers/cm 3 (190 fibers L > 20 µm), histopathological examination revealed no evidence of any inflammatory reaction either after the cessation of the last exposure or at any time during the subsequent 12-mo period. This is in marked contrast to the amphibole tremolite, which was also investigated using the same inhalation biopersistence protocol. The long tremolite fibers, once deposited in the lung, remain over the rat’s lifetime with essentially an infinite half-time. Even the shorter fibers, following early clearance, also remain with no dissolution or further removal. At 365 days postexposure, there was a mean lung burden was of 0.5 million fibers L > 20 µm and 7 million fibers 5-20 µm in length with a total mean lung burden of 19.6 million fibers. The tremolite exposed rats, even with exposure to 16 times fewer total fibers than chrysotile, showed a pronounced inflammatory response with the rapid development of granulomas as seen at day 1 postexposure, followed by the development of fibrosis characterized by collagen deposition within these granulomas and by 90 days even mild interstitial fibrosis. With the short exposure, this study was not designed specifically to evaluate pathological response. however, it is quite interesting that even so there was such a marked response with tremolite. These findings provide an important basis for substantiating both kinetically and pathologically the differences between chrysotile and the amphibole tremolite. As Calidria chrysotile has been certified to have no tremolite fiber, the results of the current study together with the results from toxicological and epidemiological studies indicate that this fiber is not associated with lung disease.

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.

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.