Abstract:
BACKGROUND:The incidence of asbestos-induced human cancers is increasing worldwide, and considerable evidence suggests that reactive oxygen species (ROS) are important mediators of these diseases. Our previous studies suggested that mitochondria might be involved in the initiation of oxidative stress in asbestos-exposed mammalian cells. OBJECTIVE:We investigated whether mitochondria are a potential cytoplasmic target of asbestos using a mitochondrial DNA-depleted (ρ(0)) human small airway epithelial (SAE) cell model: ρ(0) SAE cells lack the capacity to produce mitochondrial ROS. METHODS:We examined nuclear DNA damage, micronuclei (MN), intracellular ROS production, and the expression of inflammation-related nuclear genes in both parental and ρ(0) SAE cells in response to asbestos treatment. RESULTS:Asbestos induced a dose-dependent increase in nuclear DNA oxidative damage and MN in SAE cells. Furthermore, there was a significant increase in intracellular oxidant production and activation of genes involved in nuclear factor κB and proinflammatory signaling pathways in SAE cells. In contrast, the effects of asbestos were minimal in ρ(0) SAE cells. CONCLUSIONS:Mitochondria are a major cytoplasmic target of asbestos. Asbestos may initiate mitochondria-associated ROS, which mediate asbestos-induced nuclear mutagenic events and inflammatory signaling pathways in exposed cells. These data provide new insights into the molecular mechanisms of asbestos-induced genotoxicity.
journal_name
Environ Health Perspectjournal_title
Environmental health perspectivesauthors
Huang SX,Partridge MA,Ghandhi SA,Davidson MM,Amundson SA,Hei TKdoi
10.1289/ehp.1104287subject
Has Abstractpub_date
2012-06-01 00:00:00pages
840-7issue
6eissn
0091-6765issn
1552-9924journal_volume
120pub_type
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journal_title:Environmental health perspectives
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journal_title:Environmental health perspectives
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journal_title:Environmental health perspectives
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更新日期:1994-09-01 00:00:00
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journal_title:Environmental health perspectives
pub_type: 共识发展会议,杂志文章,评审
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更新日期:1994-12-01 00:00:00
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更新日期:1999-05-01 00:00:00
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journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.898243
更新日期:1989-07-01 00:00:00
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更新日期:2017-08-01 00:00:00
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pub_type: 杂志文章
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更新日期:1993-10-01 00:00:00
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journal_title:Environmental health perspectives
pub_type: 杂志文章,评审
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更新日期:1995-09-01 00:00:00
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journal_title:Environmental health perspectives
pub_type: 杂志文章
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更新日期:1993-12-01 00:00:00
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更新日期:2005-04-01 00:00:00
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更新日期:2008-10-01 00:00:00
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journal_title:Environmental health perspectives
pub_type: 杂志文章,评审
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更新日期:1985-10-01 00:00:00
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更新日期:2010-03-01 00:00:00
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journal_title:Environmental health perspectives
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更新日期:1995-02-01 00:00:00