Dose-Response Relationships in Expression of Biomarkers of Cell Proliferation in Assays and Inhalation Experiments

Asbestos is a group of naturally occurring mineral fibers which are associated in occupational settings with increased risks of malignant mesothelioma (MM), lung cancers, and pulmonary fibrosis (asbestosis). The six recognized types of asbestos fibers (chrysotile, crocidolite, amosite, tremolite, an...

Full description

Bibliographic Details
Main Authors: Arti Shukla, Pamela Vacek, Brooke T. Mossman
Format: Article
Language:English
Published: SAGE Publishing 2004-04-01
Series:Dose-Response
Online Access:https://doi.org/10.1080/15401420490464420
_version_ 1819057198761771008
author Arti Shukla
Pamela Vacek
Brooke T. Mossman
author_facet Arti Shukla
Pamela Vacek
Brooke T. Mossman
author_sort Arti Shukla
collection DOAJ
description Asbestos is a group of naturally occurring mineral fibers which are associated in occupational settings with increased risks of malignant mesothelioma (MM), lung cancers, and pulmonary fibrosis (asbestosis). The six recognized types of asbestos fibers (chrysotile, crocidolite, amosite, tremolite, anthophyllite, and actinolite) are different chemically and physically and may have different dose-response relationships in the development of various asbestos-associated diseases. For example, epidemiologic and lung fiber content studies suggest that the pathogenic potential and durability of crocidolite is much greater than chrysotile asbestos in the causation of human MM. We have used isolated mesothelial cells, the target cells of MM, as well as epithelial cells of the lung, the target cells of lung cancers, in vitro to elucidate the dose-response relationships in expression of early response protooncogenes and other genes critical to cell proliferation and malignant transformation in cells exposed to crocidolite and chrysotile asbestos, as well as a number of nonpathogenic fibers and particles. These studies reveal distinct dose-response patterns with different types of asbestos, suggesting a threshold for effects of chrysotile both in in vitro studies and inhalation experiments. The different patterns of gene expression have been confirmed in lungs of rats exposed by inhalation to these types of asbestos. Experiments also suggest no observed adverse effect levels after evaluation of lung injury, inflammation, and fibrosis at lower concentrations of both types of asbestos.
first_indexed 2024-12-21T13:35:30Z
format Article
id doaj.art-bd19040477d245ee9ea6c7b263b8bf98
institution Directory Open Access Journal
issn 1559-3258
language English
last_indexed 2024-12-21T13:35:30Z
publishDate 2004-04-01
publisher SAGE Publishing
record_format Article
series Dose-Response
spelling doaj.art-bd19040477d245ee9ea6c7b263b8bf982022-12-21T19:02:10ZengSAGE PublishingDose-Response1559-32582004-04-01210.1080/15401420490464420Dose-Response Relationships in Expression of Biomarkers of Cell Proliferation in Assays and Inhalation ExperimentsArti ShuklaPamela VacekBrooke T. MossmanAsbestos is a group of naturally occurring mineral fibers which are associated in occupational settings with increased risks of malignant mesothelioma (MM), lung cancers, and pulmonary fibrosis (asbestosis). The six recognized types of asbestos fibers (chrysotile, crocidolite, amosite, tremolite, anthophyllite, and actinolite) are different chemically and physically and may have different dose-response relationships in the development of various asbestos-associated diseases. For example, epidemiologic and lung fiber content studies suggest that the pathogenic potential and durability of crocidolite is much greater than chrysotile asbestos in the causation of human MM. We have used isolated mesothelial cells, the target cells of MM, as well as epithelial cells of the lung, the target cells of lung cancers, in vitro to elucidate the dose-response relationships in expression of early response protooncogenes and other genes critical to cell proliferation and malignant transformation in cells exposed to crocidolite and chrysotile asbestos, as well as a number of nonpathogenic fibers and particles. These studies reveal distinct dose-response patterns with different types of asbestos, suggesting a threshold for effects of chrysotile both in in vitro studies and inhalation experiments. The different patterns of gene expression have been confirmed in lungs of rats exposed by inhalation to these types of asbestos. Experiments also suggest no observed adverse effect levels after evaluation of lung injury, inflammation, and fibrosis at lower concentrations of both types of asbestos.https://doi.org/10.1080/15401420490464420
spellingShingle Arti Shukla
Pamela Vacek
Brooke T. Mossman
Dose-Response Relationships in Expression of Biomarkers of Cell Proliferation in Assays and Inhalation Experiments
Dose-Response
title Dose-Response Relationships in Expression of Biomarkers of Cell Proliferation in Assays and Inhalation Experiments
title_full Dose-Response Relationships in Expression of Biomarkers of Cell Proliferation in Assays and Inhalation Experiments
title_fullStr Dose-Response Relationships in Expression of Biomarkers of Cell Proliferation in Assays and Inhalation Experiments
title_full_unstemmed Dose-Response Relationships in Expression of Biomarkers of Cell Proliferation in Assays and Inhalation Experiments
title_short Dose-Response Relationships in Expression of Biomarkers of Cell Proliferation in Assays and Inhalation Experiments
title_sort dose response relationships in expression of biomarkers of cell proliferation in assays and inhalation experiments
url https://doi.org/10.1080/15401420490464420
work_keys_str_mv AT artishukla doseresponserelationshipsinexpressionofbiomarkersofcellproliferationinassaysandinhalationexperiments
AT pamelavacek doseresponserelationshipsinexpressionofbiomarkersofcellproliferationinassaysandinhalationexperiments
AT brooketmossman doseresponserelationshipsinexpressionofbiomarkersofcellproliferationinassaysandinhalationexperiments