Human & Experimental Toxicology

Our medical research library holds 8 studies published in Human & Experimental Toxicology (1992–2021). 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. 8 have an abstract, the authors' own summary as PubMed records it: open "Abstract" to read it.

About the journal

• Publisher: SAGE Publications
• Published: 1990 to the present, England
• Language: English
• ISSN: 0960-3271 (print), 1477-0903 (electronic)
• Continues: Human Toxicology
• Its record in the NLM Catalog

2020s

• The usefulness of biomarkers in diagnosis of asbestos-induced malignant pleural mesothelioma. Z. Tanrıverdi, F. Meteroglu, H. Yüce, et al. 2021;40(11):1817-1824. PubMed · Publisher

  Abstract

  Introduction: Malignant pleural mesothelioma (MPM) is a malignant tumor that is associated mostly with asbestos exposure. The present study was to evaluates the diagnostic value of neopterin, periostin, YKL-40, Tenascin-C (TNC), and Indolamine 2,3-dioxygenase (IDO) as noninvasive markers of malign pleural mesothelioma.

  Methods: Included in the study were 30 patients diagnosed with malign pleural mesothelioma, and 25 people as a control group. Biomarker levels were determined using an enzyme immunoassay . A Mann-Whitney U test and Spearman correlation methods were used for the statistical analysis.

  Results: All evaluated biomarkers were found to be significantly higher in the MPM group than in the control group (p < 0.05). There was no effect of such variables as gender, age or MPMsubtype on the parameters (p > 0.05) in the patient group. All biomarkers were positively correlated with each other (p < 0.001).

  Conclusions: The current non-invasive biomarkers that can be used in the diagnosis of MPM yielded significant results and can make important contributions to the early diagnosis of MPM.

• Difficulties in establishing a causal link between chemical exposures and cancer cannot be overcome by court assessments. T.A. Dragani. 2020;39(8):1095-1107. PubMed · Publisher

  Abstract

  Scientific data are often used in lawsuits to prove, or dismiss, causation by a claimed factor of a claimed disease. Recent media reports of million-dollar compensations awarded to some cancer patients who had been exposed to certain chemical substances motivated me to examine how solid the causal links really were. Here, I discuss the limitations of epidemiological research on cancer causation and highlight how new knowledge of cancer genetics makes it unrealistic to expect that cancer causation can be clearly demonstrated. I then present two exposure-cancer cases, namely talcum powder-ovarian cancer and glyphosate-non-Hodgkin lymphoma, that led to civil lawsuits decided, in the United States, in favor of the claimants. Both these cancers have several risk factors, among which the claimed exposure presents only a minor, if any, increased risk. Through these cases, I explain why the use of epidemiological data is inappropriate to define causal associations in complex diseases like cancer. I close by suggesting a fairer approach, called proportional liability, to resolving future cancer litigation cases.

2010s

• EF24 and RAD001 potentiates the anticancer effect of platinum-based agents in human malignant pleural mesothelioma (MSTO-211H) cells and protects nonmalignant mesothelial (MET-5A) cells. H.I. Onen, A. Yilmaz, E. Alp, et al. 2015;34(2):117-26. PubMed · Publisher

  Abstract

  The most widespread neoplasm of the pleura is malignant pleural mesothelioma (MPM) with low prevalence rate. The mechanistic target of rapamycin signaling pathway, inhibited by RAD001, was shown to be deregulated in MPM development and considered a novel target for the MPM therapy. The EF24, a curcumin analog, also affects several signaling pathways and kills cancer cells as a single agent or in combination with classical drugs. We aimed to evaluate possible effects of RAD001, EF24, cisplatin, and oxaliplatin treatments on both malignant pleural mesothelioma (MSTO-211H) and nonmalignant mesothelial (Met-5A) cell lines. The effects of the agents on MSTO-211H and Met-5A cells were evaluated in terms of cell viability, cytotoxicity, DNA synthesis rate, quantitation of apoptotic DNA fragmentation, and cleaved caspase 3 levels. Moreover, quantitative messenger RNA (mRNA) analysis of apoptotic (CASP9) and antiapoptotic (BCL2L1 and BCL2) genes were also performed. We found that both EF24 and RAD001 alone treatments decreased only MSTO-211H cell viability, but cisplatin and oxaliplatin affected both cell lines. Pretreatment with EF24 or RAD001 followed by cisplatin increased the effects of cisplatin alone application. EF24 and RAD001 pretreatment decreased DNA fragmentation rate when compared with cisplatin alone treatment in Met-5A cells. Sequential treatments resulted in a significant increase of CASP9 mRNA expression in MSTO-211H cells but not in Met-5A cells. Our preliminary results suggest that pretreatment with EF24 or RAD001 may reduce cytotoxic effect of cisplatin on nonmalignant mesothelial cells and increase cell death response of MPM cells. Further analyses using animal models are needed to confirm these findings in vivo.

  © The Author(s) 2015.

1990s

• Production of reactive oxygen species by man-made vitreous fibres in human polymorphonuclear leukocytes. M. Ruotsalainen, M.R. Hirvonen, K. Luoto, et al. 1999;18(6):354-62. PubMed · Publisher

  Abstract

  Human polymorphonuclear leukocytes (PMNL) or erythrocytes, isolated from human blood, were exposed to graded doses of asbestos (chrysotile), quartz, or man-made vitreous fibres (MMVF), i.e. refractory ceramic fibres (RCF), glasswool, or rockwool fibres. None of the MMVF affected either the viability of PMNL, as measured by trypan blue exclusion test, or induced haemolysis, whereas the positive controls, quartz and chrysotile, dose-dependently induced haemolysis in PMNL. MMVF did not increase the release of lactate dehydrogenase (LDH) from the PMNL, whereas the positive controls, chrysotile and quartz, induced a marked and dose-dependent release of LDH. When PMNL were exposed to MMVF, some of the fibre types slightly increased the levels of free intracellular calcium ([Ca2+]i) within the cells in a manner similar to that induced by chrysotile or quartz. All MMVF induced a dose-dependent production of reactive oxygen species (ROS) in PMNL, with RCF-induced production of ROS being the most marked. Production of ROS by MMVF seemed to depend on the availability of extracellular calcium because it could be attenuated with a Ca2+ channel blocker, verapamil, or a Ca2+ chelating agent, EGTA. Production of ROS may be a common pathway through which PMNL respond to MMVF-induced cell activation, but alterations of levels of free intracellular Ca2+ do not seem to be an absolute prerequisite for this effect. Fibre length seemed not to be an important factor in affecting the ability of MMVF to induce ROS production in PMNL. However, the balance between different elements in the fibre seemed importantly to affect the biological activity of a fibre.

• Evaluating chemical risks: results of a survey of the British Toxicology Society. P. Slovic, T. Malmfors, C.K. Mertz, et al. 1997;16(6):289-304. PubMed · Publisher

  Abstract

  1. Members of the British Toxicology Society participated in a survey to determine their attitudes, beliefs, and perceptions regarding risks from chemicals. Similar surveys had previously been conducted with toxicologists and members of the general public in the United States and Canada. Data from 312 completed questionnaires were analyzed. 2. In general, the British toxicologists judged risks to be quite low for most hazards, with the exception of cigarette smoking and asbestos. They tended to have quite favorable attitudes toward the use of chemicals and were confident about the adequacy of chemical regulations. 3. As in previous studies of toxicologists, women expressed higher perceptions of risk than did men and had consistently stronger anti-chemical attitudes. 4. Toxicologists working in industry had more favorable attitudes towards chemicals and their use than did those working in academic settings. 5. When asked to evaluate chemical technical summaries of various animals studies there was considerable disagreement among the respondents about the toxicity of the chemicals involved. 6. In general, British toxicologists were equivocal about the reliability of animal studies in predicting human effects (particularly carcinogenicity) probably because of the belief that animal studies overestimate risk. However, they were rather confident that human health risks could be assessed reasonably accurately.

• Effects of a protein kinase C inhibitor, Ro 31-7549, on the activation of human leukocytes by particulate stimuli. M. Ruotsalainen, K.M. Savolainen. 1995;14(3):266-72. PubMed · Publisher

  Abstract

  1. A new specific protein kinase C (PKC) inhibitor, Ro 31-7549, was used to explore the mechanisms by which particulate stimuli, quartz and chrysotile, stimulate human polymorphonuclear leukocytes (PMNL) to produce reactive oxygen metabolites (ROM). Also soluble stimuli, formyl-Methionyl-Leucyl-Phenylalanine (fMLP) and phorbol myristate acetate (PMA) were used. 2. Ro 31-7549 inhibited chrysotile-induced free intracellular calcium ([Ca2+]i) elevations but did not have an effect on quartz-induced elevations of [Ca2+]i. Both quartz and chrysotile induced production of ROM were partially inhibited by Ro 31-7549. fMLP-induced elevation of [Ca2+]i was inhibited by Ro 31-7549 whereas PMA did not affect [Ca2+]i. Ro 31-7549 strongly inhibited fMLP-induced ROM production, and completely abolished that induced by PMA. 3. These result suggest that PKC may have an important role in the activation of PMNL to produce ROM by particulate and soluble stimuli. However, the inhibition of chrysotile-, but not of quartz-induced [Ca2+]i elevations by Ro 31-7549 provides evidence that both PKC-dependent and -independent mechanisms may play a role in the activation of human leukocytes to produce ROM.

• Increased incidence of DNA double-strand breaks and anti-ds DNA antibodies in blood of workers occupationally exposed to asbestos. B. Marczynski, A.B. Czuppon, W. Marek, et al. 1994;13(1):3-9. PubMed · Publisher

  Abstract

  Asbestos, proven to be carcinogenic in humans and animals, is reported to have no genotoxic effect. Asbestos workers have an increased risk of lung cancer, mesothelioma, and other tumours. Earlier findings showed that crocidolite can induce DNA strand breaks in cultured rat embryo cells as assessed by nick translation. We investigated DNA double-strand breaks in white blood cells (WBC) of ten workers occupationally exposed to asbestos. According to our results, obtained with neutral filter elution, individuals who had been exposed to asbestos fibres showed two to four times more DNA double-strand breaks (dsb) in white blood cells than ten non-exposed persons. The induced DNA fragments are of about 250 kb (compared to chromosomal DNA of Saccharomyces cerevisiae standard marker). Using additionally the chromosomal DNA protective method of agarose-plugs, DNA fragments in the range of 200 to 1000 kb have been found in the white blood cells of the same ten workers occupationally exposed to asbestos. In the white blood cells of non-exposed subjects no DNA fragments could be detected with this method. Compared to 51 non-exposed persons, elevated anti-ds DNA antibody concentrations were found in ten workers occupationally exposed to asbestos. The fact that workers occupationally exposed to asbestos have distinctly more double-strand breaks and anti-ds DNA antibodies could mean that an increased incidence of DNA-fragments may be an important indicator in the chronic effect of asbestos-associated carcinogenesis. Apparently, the chronic effects of asbestos observed here do not seem to be identical with that of previously reported acute in vitro effects.

• Intrapleural administration of fibres induces mesothelioma in rats in the same relative order of hazard as occurs in man after exposure. P. Carthew, R.J. Hill, R.E. Edwards, et al. 1992;11(6):530-4. PubMed · Publisher

  Abstract

  1. The dose-response data for the induction of mesothelioma, in rats, by the intrapleural administration of the fibrous zeolite, erionite, has been compared to the published data for the crocidolite and chrysotile forms of asbestos. Erionite is more than two orders of magnitude more carcinogenic than either of the two forms of asbestos examined. 2. The relative sensitivity of the intrapleural and intraperitoneal routes of injection were also examined. The sensitivity of the intraperitoneal over the intrapleural route of administration was considerably greater for all the forms of asbestos examined but not for erionite. 3. The relationship for different fibres, between the number of fibres required to give animals mesothelioma, at the 50% or 10% observable tumour effect level (OTEL) was examined, and a ranking of relative carcinogenicity was made. 4. This showed that the data derived from the dose responses obtained by the intrapleural administration of fibres to rats ranked the relative carcinogenicity of erionite, crocidolite and chrysotile in accord with the known clinical mesothelioma induction in man after exposure to these fibres. Examination of the carcinogenicity ranking from data derived from intraperitoneal injections of fibres was not in accord with the known clinical mesothelioma induction in man for the various asbestos types examined.

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