Cancer Letters

Our medical research library holds 30 studies published in Cancer Letters (1979–2024). Each entry links to the study's record on PubMed and, where there is one, to the publisher's page and a free full text. 30 have an abstract, the authors' own summary as PubMed records it: open "Abstract" to read it.

About the journal

• Publisher: Elsevier Science Ireland
• Published: 1975 to the present, Ireland
• Language: English
• ISSN: 0304-3835 (print), 1872-7980 (electronic)
• Its record in the NLM Catalog

2020s

• Linc00941 fuels ribogenesis and protein synthesis by supporting robust cMYC translation in malignant pleural mesothelioma. M. Gugnoni, E. Lorenzini, F. Torricelli, et al. 2024;592:216950. PubMed · Publisher

  Abstract

  Malignant pleural mesothelioma is a rare and lethal cancer caused by exposure to asbestos. The highly inflammatory environment caused by fibers accumulation forces cells to undergo profound adaptation to gain survival advantages. Prioritizing the synthesis of essential transcripts is an efficient mechanism coordinated by multiple molecules, including long non-coding RNAs. Enhancing the knowledge about these mechanisms is an essential weapon in combating mesothelioma. Linc00941 correlates to bad prognosis in various cancers, but it is reported to partake in distinct and apparently irreconcilable processes. In this work, we report that linc00941 supports the survival and aggressiveness of mesothelioma cells by influencing protein synthesis and ribosome biogenesis. Linc00941 binds to the translation initiation factor eIF4G, promoting the selective protein synthesis of cMYC, which, in turn, enhances the expression of key genes involved in translation. We analyzed a retrospective cohort of 97 mesothelioma patients' samples from our institution, revealing that linc00941 expression strongly correlates with reduced survival probability. This discovery clarifies linc00941's role in mesothelioma and proposes a unified mechanism of action for this lncRNA involving the selective translation of essential oncogenes, reconciling the discrepancies about its function.

  Copyright © 2024 Elsevier B.V. All rights reserved.

• Targeting YB-1 via entinostat enhances cisplatin sensitivity of pleural mesothelioma in vitro and in vivo. K. Schelch, D. Emminger, B. Zitta, et al. 2023;574:216395. PubMed · Publisher

  Abstract

  Pleural mesothelioma (PM) is characterized by poor prognosis and limited therapeutic options. Y-box-binding protein 1 (YB-1) was shown to drive growth and migration of PM cells. Here, we evaluated the effect of genetic and pharmacological targeting of YB-1 on PM growth and response to cisplatin and radiation treatment. YB-1 knockdown via siRNA resulted in reduced PM cell growth, which significantly correlated with wt BAP1 and mutant NF2 and P53 status. Entinostat inhibited YB-1 deacetylation and its efficacy correlated with YB-1 knockdown-induced growth inhibition in 20 PM cell lines. Tumor growth inhibition by siRNA as well as entinostat was confirmed in mouse xenotransplant models. Furthermore, both YBX1-targeting siRNA and entinostat enhanced sensitivity to cisplatin and radiation. In particular, entinostat showed strong synergistic interactions with cisplatin which was linked to significantly increased cellular platinum uptake in all investigated cell models. Importantly, in a mouse model, the combination of cisplatin and entinostat also resulted in stronger growth inhibition than each treatment alone. Our study highlights YB-1 as an attractive target in PM and demonstrates that targeting YB-1 via entinostat is a promising approach to enhance cisplatin and radiation sensitivity.

  Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.

• Endogenous retrovirus expression activates type-I interferon signaling in an experimental mouse model of mesothelioma development. S. Sun, F. Frontini, W. Qi, et al. 2021;507:26-38. PubMed · Publisher

  Abstract

  Early events in an experimental model of mesothelioma development include increased levels of editing in double-stranded RNA (dsRNA). We hypothesised that expression of endogenous retroviruses (ERV) contributes to dsRNA formation and type-I interferon signaling. ERV and interferon stimulated genes (ISGs) expression were significantly higher in tumor compared to non-tumor samples. 12 tumor specific ERV ("MesoERV1-12") were identified and verified by qPCR in mouse tissues. "MesoERV1-12" expression was lower in mouse embryonic fibroblasts (MEF) compared to mesothelioma cells. "MesoERV1-12" levels were significantly increased by demethylating agent 5-Aza-2'-deoxycytidine treatment and were accompanied by increased levels of dsRNA and ISGs. Basal ISGs expression was higher in mesothelioma cells compared to MEF and was significantly decreased by JAK inhibitor Ruxolitinib, by blocking Ifnar1 and by silencing Mavs. "MesoERV7" promoter was demethylated in asbestos-exposed compared to sham mice tissue as well as in mesothelioma cells and MEF upon 5-Aza-CdR treatment. These observations uncover novel aspects of asbestos-induced mesothelioma whereby ERV expression increases due to promoter demethylation and is paralleled by increased levels of dsRNA and activation of type-I IFN signaling. These features are important for early diagnosis and therapy.

  Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.

2010s

• Germline mutations in DNA repair genes predispose asbestos-exposed patients to malignant pleural mesothelioma. M. Betti, E. Casalone, D. Ferrante, et al. 2017;405:38-45. PubMed · Publisher

  Abstract

  Malignant pleural mesothelioma (MPM) is a rare, aggressive cancer caused by asbestos exposure. An inherited predisposition has been suggested to explain multiple cases in the same family and the observation that not all individuals highly exposed to asbestos develop the tumor. Germline mutations in BAP1 are responsible for a rare cancer predisposition syndrome that includes predisposition to mesothelioma. We hypothesized that other genes involved in hereditary cancer syndromes could be responsible for the inherited mesothelioma predisposition. We investigated the prevalence of germline variants in 94 cancer-predisposing genes in 93 MPM patients with a quantified asbestos exposure. Ten pathogenic truncating variants (PTVs) were identified in PALB2, BRCA1, FANCI, ATM, SLX4, BRCA2, FANCC, FANCF, PMS1 and XPC. All these genes are involved in DNA repair pathways, mostly in homologous recombination repair. Patients carrying PTVs represented 9.7% of the panel and showed lower asbestos exposure than did all the other patients (p = 0.0015). This suggests that they did not efficiently repair the DNA damage induced by asbestos and leading to carcinogenesis. This study shows that germline variants in several genes may increase MPM susceptibility in the presence of asbestos exposure and may be important for specific treatment.

  Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

• CDKN2A and BAP1 germline mutations predispose to melanoma and mesothelioma. M. Betti, A. Aspesi, A. Biasi, et al. 2016;378(2):120-30. PubMed · Publisher

  Abstract

  BAP1 germline mutations predispose to a cancer predisposition syndrome that includes mesothelioma, cutaneous melanoma, uveal melanoma and other cancers. This co-occurrence suggests that these tumors share a common carcinogenic pathway. To evaluate this hypothesis, we studied 40 Italian families with mesothelioma and/or melanoma. The probands were sequenced for BAP1 and for the most common melanoma predisposition genes (i.e. CDKN2A, CDK4, TERT, MITF and POT1) to investigate if these genes may also confer susceptibility to mesothelioma. In two out of six families with both mesothelioma and melanoma we identified either a germline nonsense mutation (c.1153C > T, p.Arg385*) in BAP1 or a recurrent pathogenic germline mutation (c.301G > T, p.Gly101Trp) in CDKN2A. Our study suggests that CDKN2A, in addition to BAP1, could be involved in the melanoma and mesothelioma susceptibility, leading to the rare familial cancer syndromes. It also suggests that these tumors share key steps that drive carcinogenesis and that other genes may be involved in inherited predisposition to malignant mesothelioma and melanoma.

  Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

• Germline BAP1 mutation in a family with high incidence of multiple primary cancers and a potential gene-environment interaction. M. Cheung, Y. Kadariya, J. Talarchek, et al. 2015;369(2):261-5. PubMed · Publisher · Free full text

  Abstract

  We report a high-risk cancer family with multiple mesotheliomas, cutaneous melanomas, basal cell carcinomas, and meningiomas segregating with a germline nonsense mutation in BAP1 (c.1938T>A; p.Y646X). Notably, most (four of five) mesotheliomas were peritoneal rather than the usually more common pleural form of the disease, and all five mesothelioma patients also developed second or third primary cancers, including two with meningiomas. Another family member developed both cutaneous melanoma and breast cancer. Two family members had basal cell carcinomas, and six others had melanocytic tumors, including four cutaneous melanomas, one uveal melanoma, and one benign melanocytic tumor. The family resides in a subtropical area, and several members had suspected exposure to asbestos either occupationally or in the home. We hypothesize that the concurrence of a genetic predisposing factor and environmental exposure to asbestos and UV irradiation contributed to the high incidence of multiple cancers seen in this family, specifically mesothelioma and various uveal/skin tumors, respectively.

  Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

• DNA repair systems in malignant mesothelioma. D. Toumpanakis, S.E. Theocharis. 2011;312(2):143-9. Review PubMed · Publisher

  Abstract

  Malignant mesothelioma (MM) is an aggressive tumor of serosal surfaces with increasing incidence and poor prognosis. Asbestos exposure is the main cause of MM and asbestos-induced DNA damage is critical for MM pathogenesis. The present review summarizes the implications of DNA repair systems in MM development, focusing on gene expression alterations and single nucleotide polymorphisms of genes encoding for DNA repair enzymes. The involvement of DNA repair systems in MM improves understanding of MM pathogenesis and provides novel therapeutical targets.

  Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

• Knockdown of ZEB1, a master epithelial-to-mesenchymal transition (EMT) gene, suppresses anchorage-independent cell growth of lung cancer cells. Y. Takeyama, M. Sato, M. Horio, et al. 2010;296(2):216-24. PubMed · Publisher · Free full text

  Abstract

  We found that among four master epithelial-to-mesenchymal transition (EMT)-inducing genes (ZEB1, SIP1, Snail, and Slug) ZEB1expression was most significantly correlated with the mesenchymal phenotype (high Vimentin and low E-cadherin expression) in non-small cell lung cancer (NSCLC) cell lines and tumors. Furthermore, ZEB1 knockdown with RNA interference in three NSCLC cell lines with high ZEB1 expression suppressed to varying degrees mass culture growth and liquid colony formation but in all cases dramatically suppressed soft agar colony formation. In addition, ZEB1 knockdown induced apoptosis in one of the three lines, indicating that the growth inhibitory effects of ZEB1 knockdown occurs in part through the activation of the apoptosis pathway. These results suggest that inhibiting ZEB1 function may be an attractive target for NSCLC therapeutic development.

  2010 Elsevier Ireland Ltd. All rights reserved.

2000s

• Molecular and genetic changes in asbestos-related lung cancer. P. Nymark, H. Wikman, T. Hienonen-Kempas, et al. 2008;265(1):1-15. Review PubMed · Publisher

  Abstract

  Asbestos-exposure is associated with an increased risk of lung cancer, one of the leading causes of cancer deaths worldwide. Asbestos is known to induce DNA and chromosomal damage as well as aberrations in signalling pathways, such as the MAPK and NF-kappaB cascades, crucial for cellular homeostasis. The alterations result from both indirect effects through e.g. reactive oxygen/nitrogen species and direct mechanical disturbances of cellular constituents. This review describes the current knowledge on genomic and pathway aberrations characterizing asbestos-related lung cancer. Specific asbestos-associated molecular signatures can assist the development of early biomarkers, molecular diagnosis, and molecular targeted treatments for asbestos-exposed lung cancer patients.

• Manganese superoxide dismutase genotypes and asbestos-associated pulmonary disorders. A. Hirvonen, J. Tuimala, T. Ollikainen, et al. 2002;178(1):71-4. PubMed · Publisher

  Abstract

  Manganese superoxide dismutase (MnSOD) activity is highly elevated in the biopsies of human asbestos-associated malignant mesothelioma. We therefore examined if polymorphism in the mitochondrial targeting sequence of the MnSOD gene modified individual susceptibility to this malignancy or related asbestos-associated pulmonary disorders. The study population consisted of 124 male Finnish asbestos insulators who were all classified as having been exposed to high levels of asbestos; 63 of the workers had no pulmonary disorders and 61 either had malignant mesothelioma or the non-malignant pulmonary disorders asbestosis and/or pleural plaques. No significant associations were found between the MnSOD genotypes and these ill-health. This study therefore suggest no major modifying role for the MnSOD polymorphism in development of asbestos-associated pulmonary disorders.

1990s

• Mesotheliomas induced in rats by the fibrous mineral erionite are independent from p53 alterations. E.V. Kleymenova, G. Horesovsky, L.N. Pylev, et al. 1999;147(1-2):55-61. PubMed · Publisher

  Abstract

  The development of human malignant mesothelioma (MM) is strongly associated with occupational or environmental exposure to certain natural mineral fibers, although the genetic mechanisms underlying this malignancy remain unclear. Although the p53 gene is frequently mutated in various tumors, human asbestos-associated MMs appear to develop independently from p53 alterations. The high mesotheliomagenic potency of natural fibrous mineral erionite is well established in humans and rodents, but no data regarding genetic alterations in erionite-associated tumors are currently available. Previous speculations that the oncogenic mechanisms underlying asbestos and erionite carcinogenesis may differ led us to examine whether the p53 gene is targeted in erionite carcinogenesis. Fifteen erionite-induced rat MMs as well as six cell lines derived from asbestos-induced and spontaneous rat MM were analyzed for p53 mutations by direct DNA sequencing and immunohistochemical analysis. Both approaches did not reveal p53 alterations in rat MM samples used in the study indicating that, similar to asbestos carcinogenesis, erionite carcinogenesis does not target the p53 tumor suppressor gene.

• On the mechanism of cogenotoxic action between ingested amphibole asbestos fibres and benzo[a]pyrene: II. Tissue specificity studies using comet assay. C. Varga, G. Horváth, V. Timbrell. 1999;139(2):173-6. PubMed · Publisher

  Abstract

  Epidemiological data seem to be equivocal on the probable increase in cancer incidence in populations exposed to asbestos-fibre contaminated drinking water. Although animal experiments failed to demonstrate carcinogenicity of oral asbestos exposure, the large surface area of the fibres, however, creates the possibility of cogenotoxic action with adsorbed water-borne organics. In our animal model, rats were gavaged with untreated UICC crocidolite and anthophyllite fibres and fibres that had been allowed to adsorb benzo[a]pyrene molecules from aqueous solutions. Peritoneal macrophages and intestine, parietal peritoneum and omentum samples were obtained from the animals after 24 h. The alkaline single-cell microgel electrophoresis assay (comet assay) was performed on cells isolated from the solid tissues. Tail moment was applied as a basis of evaluation following image analysis. Our results indicate high levels of DNA strand breaks in the cells prepared from the omentum and intestine. We could also demonstrate a significant potentiating effect of the adsorbed carcinogen on the induction of DNA damage in the omentum. The parietal peritoneum and macrophages were not involved in the early genotoxic alterations under study. Our results support the molecular model of asbestos cocarcinogenesis, including both asbestos-induced deletions and mutations caused by a mutagen carried by the same fibres.

• Familial pleural malignant mesothelioma: clustering in three sisters and one cousin. V. Ascoli, C.C. Scalzo, C. Bruno, et al. 1998;130(1-2):203-7. PubMed · Publisher

  Abstract

  Malignant mesothelioma is associated with asbestos, yet its occurrence in genetically-related individuals suggests a role of host predisposition. We have identified a cluster of pleural malignant mesothelioma in three sisters and one cousin (male). The women had worked in the same confectionery shop as pastry cooks and/or pastry shop assistants; the use of an asbestos-insulated oven was the putative source of exposure. The man had occupational exposure as a heating system installation worker. The family history reported malignant cancers in first-degree (larynx, brother; pleura and lung, mother), second-degree (lung, aunt and uncle) and third-degree (lung, cousin) relatives. The study reveals the potential existence of the mesothelioma risk among pastry cooks and highlights the fact that inherited factors may be involved in the development of this tumour.

• On the mechanism of cogenotoxic action between ingested amphibole asbestos fibres and benzo[a]pyrene: I. Urinary and serum mutagenicity studies with rats. C. Varga, G. Horváth, Z. Pocsai, et al. 1998;128(2):165-9. PubMed · Publisher

  Abstract

  Recently, there has been concern that ingested asbestos may cause an increase in cancer incidence in populations exposed to fibre-contaminated drinking water. Although animal experiments failed to demonstrate carcinogenicity of the oral asbestos exposure, the high adsorption capacity of the fibres creates the possibility of cocarcinogenic action with adsorbed organics. In a simple in vivo model we demonstrated earlier that UICC crocidolite and anthophyllite asbestos fibres were able to adsorb carcinogen molecules from aqueous solutions. When orally administered, these fibres increased the sister chromatid exchange frequency in bone marrow cells of rats. In the present study we tried to follow the desorption and metabolization processes of carcinogenic benzo[a]pyrene molecules transported by the ingested fibres using the highly sensitive Salmonella/Ames mutagenicity assay. The bacterial test was performed on concentrated serum and urine samples of the treated animals by using the TA98 and 100 strains in the presence and absence of liver microsomal and deconjugating enzymes. All sets of urine and serum samples failed to show mutagenic activity indicating a lack of both desorption in the serum and the ability of the liver to metabolize. Considering our results, the cytogenetic impact demonstrated earlier in the bone marrow can be explained by a local action of accumulated and transported carcinogen molecules.

• Pathogenesis of experimentally induced asbestos mesothelioma in rats. L.A. Vasilieva, L.N. Pylev, Y.A. Rovensky. 1998;134(2):209-16. PubMed · Publisher

  Abstract

  Fragments of parietal and visceral pleura were studied by total films preparation, light microscopy and SEM at different times after intrapleural injection of asbestos in Wistar rats. Pleural rat mesothelium in histological slices consists normally of one layer of oblong cells. By SEM the cells are flat and coated with microvilli of different lengths. In total films the parietal mesothelium was composed of large polygonal cells covering intercostal spaces and small cells covering spaces over the ribs. Inflammatory reaction and permanent pathological regenerative processes were observed in the mesothelium during 24 months after inoculation of asbestos fibres. Different lesions which we regarded as preneoplastic or premesotheliomatous were observed against the background of or without these processes. They were diffuse irregular hyperplasia and proliferation of epithelium-like or fibroblast-like cells and focal nodous proliferates composed of such cells with various morphological structures. The number of thymidine-labelled cells was significantly more inside the proliferates than in the surrounding tissue. They were confirmed by SEM and histological slices of the same fields. Chronic pathological regeneration of pleural mesothelium could be the background against which preneoplastic lesions and mesotheliomas develop easily.

• In vivo studies on genotoxicity and cogenotoxicity of ingested UICC anthophyllite asbestos. C. Varga, G. Horváth, V. Timbrell. 1996;105(2):181-5. PubMed · Publisher

  Abstract

  Early cytogenetic action of oral exposure to UICC anthophyllite, an amphibole type of asbestos, was studied in Fischer-344 rats. The animals were gavaged with a suspension of untreated fibres (50 mg/kg) and fibres which had been allowed to adsorb benzo[alpha]pyrene molecules from aqueous solutions of 0.25-2.5 micrograms/ml. HPLC measurements indicated effective adsorption of the benzo[alpha]pyrene molecules on the fibres. The authors consider this system a suitable model for the drinking of water containing asbestos fibres and organic micropollutants. The formation of micronuclei and sister chromatid exchanges was studied in bone marrow samples taken from animals 24 h after oral administration of suspensions. Whereas anthophyllite fibres failed to induce cytogenetic alterations, fibres pretreated with the polycyclic aromatic solutions caused dose-dependent increase in the sister chromatid exchange frequencies. The observed cytogenetic impact can be explained by a local action of carcinogen molecules accumulated and subsequently transported. The results support the hypothesis that epidemiological evidence of carcinogenicity of asbestos in potable water may rather be explained by cogenotoxic action of the asbestos fibres and biologically active organic micropollutants adsorbed on their surface.

• Malignant tumours of the gastrointestinal tract in an area with an asbestos-cement plant. M. Sarić, K. Curin. 1996;103(2):191-9. PubMed · Publisher

  Abstract

  Data on persons who died of cancer of the gastrointestinal tract in a Croatian coastal area with an asbestos-cement plant were analysed for the period 1970-1990. By poll method applied to the families of deceased subjects, additional data on occupation, lifestyle, educational level, length of resistance and cancer mortality among relatives were collected. The investigation showed that in the study area, but also in certain narrower locations within it (subarea settlements), some of the tumours studied occurred at higher rates than expected. Although not conclusive, these findings may indicate a role of environmental exposure to asbestos, particularly in the occurrence of peritoneal mesothelioma.

• Parental cancer and genetic predisposition in malignant pleural mesothelioma: a case-control study. M. Huncharek, K. Kelsey, J. Muscat, et al. 1996;102(1-2):205-8. PubMed · Publisher

  Abstract

  Familial clustering of pleural mesothelioma (PM) has been previously reported suggesting that genetic factors (predisposition) may be involved in PM. We studied parental cancer history in a cohort of 39 cases of PM and 259 age matched controls to assess the possible influence of family history on PM risk. Cases consisted of 39 patients with PM treated at our institution between 1978 and 1993. An age frequency matched control group (by 5-year age groups) consisted of 259 subjects who were spouses or friends of patients undergoing resection of primary lung cancer. Data were obtained by interview of controls and interview of the patient or next of kin (usually spouse) for cases. The following data were obtained using a standard questionnaire and medical record review; age, sex, date of diagnosis, history of asbestos exposure, smoking history, method of diagnosis, histologic subtype, type of treatment, parental cancer history and tumor type. Cases and control frequency of parental cancer and site specific tumor frequency were compared using chi-square analysis. Twenty-eight (71%) cases reported a parental history of cancer versus 114 (44%) in the control group (P<0.01). Gastrointestinal malignancies were the predominant tumor type among parents of cases, i.e. 11 cases (40%) versus 25% of controls (P<0.01). No other tumor site showed an increased frequency among cases. These data suggest a possible role for family history in the development of PM. Genetic predisposition may be important in the etiology of this tumor.

• Asbestos induces aberrant crypt foci in the colon of rats. D.E. Corpet, V. Pirot, I. Goubet. 1993;74(3):183-7. PubMed · Publisher

  Abstract

  The carcinogenicity of asbestos to the gut is controversial. The aberrant crypt focus (ACF) assay is proposed as a test for colon carcinogens. We have scored ACF in the colon of rats and mice, one month after per os gavages with suspensions of asbestos fibers. Crocidolite asbestos induced ACF in the colon of rats in two independent experiments (P = 0.02 and P < 0.01 compared to controls given water), and was ten times less effective than the carcinogen azoxymethane. Chrysotile asbestos also induced ACF in rats. Neither crocidolite nor chrysotile induced ACF in mice. The data suggest that ingested asbestos may be carcinogenic to the colon.

• Expression of plasminogen activator and plasminogen activator inhibitor by rat mesothelioma induced by asbestos. S.P. Lenz, F.H. Green, P.G. Murphy, et al. 1993;68(2-3):119-27. PubMed · Publisher

  Abstract

  We have investigated the expression of plasminogen activators (PAs) and PA inhibitors (PAIs) by an asbestos-induced mesothelioma. Using zymographic, immunological and biochemical techniques it was demonstrated that cell lines derived from the tumor express high levels of PAI and low levels of a UK-like PA. Adherent and partially non-adherent variants of the mesothelioma expressed indistinguishable amounts of PAI and UK. Based on partial biochemical characterization, the PAI secreted by the mesothelioma cells was a set of PAIs which consisted of PAI-1 in addition to other species. These observations indicate that the difference in growth phenotype of the adherent and partially non-adherent lines was not due to detectable differences in PA and PAI expression.

• Activation of human CD4+CD45RA+ T cells by chrysotile asbestos in vitro. K. Kinugawa, A. Ueki, M. Yamaguchi, et al. 1992;66(2):99-106. PubMed · Publisher

  Abstract

  Chrysotile asbestos stimulates T lymphocyte subsets. Cell surface CD4 or CD45RA expression in peripheral blood mononuclear cells (PBMC) was downregulated after incubation with chrysotile asbestos in vitro temporarily. The percentage of CD4+CD45RA+ cells and mean fluorescence intensity in CD4 or CD45RA decreased after incubation with asbestos and returned to the original level after 24 h of incubation, which suggests that chrysotile asbestos activates CD4+CD45RA+ cells. No change was observed in CD29 expression. An increased percentage of IL-2R positive cells and an elevated intracellular Ca++ level were also indicative of the activation of PBMC by chrysotile asbestos.

• Crocidolite asbestos suppresses the differentiation of HL-60 cells induced by DMSO. A. Ueki, H. Tsushima, F. Hyodoh, et al. 1992;62(3):225-32. PubMed · Publisher

  Abstract

  This study was undertaken to determine if the biological function of inducers for cell differentiation is affected by asbestos fibers, which are sometimes deposited in human tissues. Protein kinase C activity, c-myc protein expression and cell surface CR3 expression were used as the markers of cell differentiation. The function of dimethylsulfoxide (DMSO), an inducer of cell differentiation, was suppressed by the co-culturing of crocidolite asbestos, because DMSO reacted with the hydroxyl radical released after the stimulation with crocidolite and spent itself. Superoxide dismutase (SOD) inhibited the effect of crocidolite, reacting rapidly with .O2- before the secondary release of .OH. Asbestos fibers deposited in tissues may inhibit the function of inducers which stimulate immature cells to differentiate, because such inducers frequently are also radical scavengers.

• Examination of factors that may influence disposition of benzo[a]pyrene in vivo: vehicles and asbestos. D.R. Bevan, M.R. Ulman. 1991;57(2):173-9. PubMed · Publisher

  Abstract

  Effects of vehicles and of asbestos on disposition of benzo[a]pyrene (B[a]P) were examined in vivo. [3H]B[a]P dissolved in triethylene glycol, ethyl laurate, or tricaprylin was intratracheally administered to male Sprague-Dawley rats. Excretion was most rapid when triethylene glycol was the vehicle, with 70.5% of the recovered dose appearing in bile in 6 h. Lower amounts were excreted into bile when ethyl laurate (58.4%) or tricaprylin (56.2%) were the vehicles, with comparably higher amounts remaining in lungs. When chrysotile asbestos was intratracheally instilled 24 h prior to instillation of [3H]B[a]P dissolved in triethylene glycol, the rate of excretion of radioactivity was slower than without asbestos pretreatment, with only 61.8% of the dose appearing in bile in 6 h.

1980s

• Ascorbic acid inhibits the squamous metaplasia that results from treatment of tracheal explants with asbestos or benzo[a]pyrene-coated asbestos. G. Holtz, E. Bresnick. 1988;42(1-2):23-8. PubMed · Publisher

  Abstract

  Hamster tracheal explants were maintained in culture in the presence or absence of benzo[a]pyrene (BP), crocidolite asbestos, or BP-coated crocidolite. Dose-dependent squamous metaplasia was observed in the treated samples. L-Ascorbic acid and DL-alpha-tocopherol were able to partially protect the tracheal explants from the metaplastic response induced by crocidolite. Furthermore, ascorbic acid reduced the extent of metaplasia observed in hamster tracheal explants that were exposed to BP-crocidolite.

• Effects of chrysotile asbestos on lung and pleural carcinogenesis of N-bis(2-hydroxypropyl)nitrosamine in rats. H. Katada, R. Higashiguchi, H. Maruyama, et al. 1983;17(3):313-20. PubMed · Publisher

  Abstract

  The effects of chrysotile asbestos on lung and pleural carcinogenesis by N-bis(2-hydroxypropyl)nitrosamine (DHPN) in male Wistar rats were studied. Chrysotile, 30 mg per rat, was injected into the left pleural cavity and 3 g/kg body wt. DHPN was injected once into the abdominal cavity. Lung tumors (adenoma, adenocarcinoma, squamous cell carcinoma, and combined carcinoma) occurred at the highest incidence (100%). Adenocarcinoma was seen in 4 of 11 (36%) rats killed at 35 weeks and in 6 of 12 (50%) rats killed at 52 weeks, squamous cell carcinoma occurred in 1 of 11 (9%) rats killed at 35 weeks and 3 of 12 (25%) rats killed at 52 weeks, and mixed carcinoma was seen in 1 of 12 (8%) rats killed at 52 weeks, which received chrysotile and DHPN. Adenocarcinoma was seen in 9 of 11 (82%) rats which received DHPN only and killed at 52 weeks. Mesotheliomas were seen in 2 of 11 (18%) rats, killed at 35 weeks, and 3 of 12 (25%) rats, killed at 52 weeks, which received chrysotile and DHPN. Hyaline thickening of the pleura was seen in 100% of rats receiving chrysotile. Mesothelial cell hyperplasia and adenomatous and/or fibromatous growth of the mesothelium were seen in the pleura on both sides, ranging from 36% to 50% and 31% to 64% in rats receiving chrysotile and DHPN, respectively. Asbestos bodies were seen in the pleura on both sides and in the lung.

• The influence of asbestos dust on the oncogenic transformation of C3H10T 1/2 cells. R.C. Brown, A. Poole, G.T. Fleming. 1983;18(2):221-7. PubMed · Publisher

  Abstract

  The cell transforming ability of asbestos dust was investigated using C3H10T 1/2 murine fibroblasts. In a series of experiments both crocidolite and amosite caused no increase in the number of transformed foci over that seen in cultures from untreated cells. The dusts, were, however, capable of augmenting the oncogenic effect of benzo[a]pyrene (BP). This putative synergistic effect was evident when fibres and chemicals were added to cultures as simple mixtures and when BP was adsorbed to the surface of the fibres.

• Asbestos body phagocytosis by human free alveolar macrophages. T.L. McLemore, M.L. Mace, V. Roggli, et al. 1980;9(2):85-93. PubMed · Publisher

  Abstract

  Phagocytosis of asbestos bodies by human free alveolar macrophages (FAMs) was documented employing light microscopy. This process was more carefully studied utilizing scanning electron microscopy (SEM) which demonstrated morphological and surface membrane changes in FAMs following phagocytosis of asbestos bodies. FAM viability was also evaluated following 24--72-h incubation of cells with asbestos bodies at a final concentration of 250 micrograms/ml. Slight, but significant, cytotoxicity was observed following the initial 24-h culture period (P = 0.032, paired, 2-tailed t-test). No further cytotoxicity was observed, however, when cells were further incubated for 48-h and 72-h intervals (P greater than 0.05 in all instances). These studies demonstrate asbestos bodies are readily phagocytized by cultured FAMs, and are only slightly cytotoxic to these human lung cells.

• Scanning electron microscopic examination of human asbestos bodies. M.L. Mace, T.L. McLemore, V. Roggli, et al. 1980;9(2):95-104. PubMed · Publisher

  Abstract

  Asbestos bodies represent the product of the macrophage's attempt to detoxify inhaled asbestos fibers. The process of asbestos body maturation was examined by scanning electron microscopy of material isolated from lungs of former asbestos workers. The results suggest that the progression from a membrane-bound, smooth coating of the fiber, to the typically beaded form may be caused by cracking and subsequent erosion due to the inspiratory and expiratory forces of the lung on the asbestos body.

1970s

• Aryl hydrocarbon hydroxylase induction in mitogen-stimulated lymphocytes by benzanthracene or cigarette tars adsorbed to asbestos fibers. T.L. McLemore, W.T. Jenkins, M.S. Arnott, et al. 1979;7(2-3):171-7. PubMed · Publisher

  Abstract

  Human mitogen-stimulated lymphocytes, cultured in the presence of amosite asbestos (AS), demonstrated a slight increase in aryl hydrocarbon hydroxylase (AHH) activity compared with non-induced (control) cultures (P = 0.005). A much greater increase in enzyme activity occurred following addition of the inducers benzanthracene (BA) or cigarette tars (CT) to cell cultures (P less than 0.001 in both instances). Significant enzyme induction also occurred when AS fibers were first preincubated with CT or BA, washed with acetone, then added to lymphocyte cultures (P less than 0.003 in all instances). This increase in AHH activity was not as great, however, as the induction observed when BA or CT was added to cell cultures. No further increase in enzyme activity was noted when AS and CT or AS and BA were simultaneously added to culture lymphocytes (P greater than 0.070 in all instances). The results demonstrate that polycyclic aromatic hydrocarbons (PAH), such as BA and other components of CT, are adsorbed and transported by amosite AS particles. These AS-PAH complexes are capable of inducing AHH in cultured human lymphocytes.

• Phagocytosis of asbestos fibers by human pulmonary alveolar macrophages. T. McLemore, M. Corson, M. Mace, et al. 1979;6(4-5):183-92. PubMed · Publisher

  Abstract

  Human pulmonary alveolar macrophages (PAMs) were cultured for 24--72 h with varying concentrations (0--300 microgram/ml) of amosite asbestos (AS). At lower AS concentrations, (less than 100 microgram/ml) no decrease in cell viability occurred during the first 24 h of culture. Significant cytotoxicity (P less than 0.005 in all instances) was observed, however, following incubation for 24 h with higher AS concentrations (greater than 100 microgram/ml). Even following incubation with lower concentrations of AS, significant cytotoxicity (P less than 0.006 in all instances) was observed after 48 or 72 h of culture. Scanning electron microscopy (SEM) clearly illustrates the various stages of AS phagocytosis by PAMs. SEM also documented morphological changes in PAMs following AS exposure. These included increased zeiosis and the appearance of a fibrous-like material on the surface of AS fibers following initial contact with the PAM cytoplasmic membrane. Further study of the biological interactions between AS and human cells, such as PAMs, might provide valuable information regarding the etiology of AS-related lung disorders.

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