Abstract:
:The hexavalent oxidation state of chromium [Cr(VI)] is a well-established human carcinogen, although the mechanism of cancer induction is currently unknown. Intracellular reduction of Cr(VI) forms Cr(V), which is thought to play a fundamental role in the mechanism of DNA damage by this carcinogen. Two separate pathways of DNA damage, an oxidative pathway and a metal-binding pathway, have been proposed to account for the lesions observed in cell systems. We have used a model Cr(V) complex, N,N-ethylenebis(salicylidene-animato)oxochromium(V) [Cr(V)-Salen], to investigate the oxidative pathway of DNA damage and to elucidate the lesions generated from this oxidation process. Reaction of Cr(V)-Salen with synthetic oligonucleotides produced guanine-specific lesions that were not 8-oxo-2'-deoxyguanosine, based on the inability of iridium(IV) to further oxidize these sites. Oxidation products were identified using a 7,8-dihydro-8-oxo-2'-deoxyguanosine (8-oxo-G) containing oligonucleotide to increase the yields of product for identification by electrospray ionization mass spectrometry. The guanine-based lesions observed by mass spectrometry corresponded to the lesions guanidinohydantoin and spiroiminodihydantoin. The effects of these Cr(V)-Salen-induced lesions on DNA replication fidelity was assayed using a polymerase-based misincorporation assay. These lesions produced G --> T transversion mutations and polymerase stops at levels greater than those observed for 8-oxo-G. These data suggest a model by which chromate can cause DNA damage leading to mutations and cancer.
journal_name
Environ Health Perspectjournal_title
Environmental health perspectivesauthors
Sugden KD,Martin BDdoi
10.1289/ehp.02110s5725subject
Has Abstractpub_date
2002-10-01 00:00:00pages
725-8eissn
0091-6765issn
1552-9924pii
sc271_5_1835journal_volume
110 Suppl 5pub_type
杂志文章abstract::Carbon tetrachloride produces liver cell injury in a variety of animal species. The first structurally recognizable changes occur in the endoplasmic reticulum, with alteration in ribosome-membrane interactions. Later there is an increase in intracellular fat, and the formation of tangled nets of the ergastoplasm. At n...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.761513
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journal_title:Environmental health perspectives
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journal_title:Environmental health perspectives
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pub_type: 杂志文章
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更新日期:2019-12-01 00:00:00
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更新日期:2012-08-01 00:00:00
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更新日期:2003-07-01 00:00:00
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journal_title:Environmental health perspectives
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更新日期:2017-07-20 00:00:00
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journal_title:Environmental health perspectives
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doi:10.1289/ehp.9828
更新日期:2007-05-01 00:00:00
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更新日期:2011-12-01 00:00:00
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pub_type: 杂志文章
doi:10.1289/ehp.97105s51121
更新日期:1997-09-01 00:00:00
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journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.961041296
更新日期:1996-12-01 00:00:00
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journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.99107205
更新日期:1999-03-01 00:00:00
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journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.8454111
更新日期:1984-03-01 00:00:00
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journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.9258
更新日期:2006-12-01 00:00:00
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journal_title:Environmental health perspectives
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更新日期:2000-08-01 00:00:00
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journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.94102s1205
更新日期:1994-01-01 00:00:00
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journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.101-1521117
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
doi:10.1289/EHP1788
更新日期:2017-06-20 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:2017-04-01 00:00:00
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journal_title:Environmental health perspectives
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更新日期:1999-04-01 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:1998-11-01 00:00:00
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journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.834993
更新日期:1983-03-01 00:00:00
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journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.01109833
更新日期:2001-08-01 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:1999-10-01 00:00:00
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pub_type: 杂志文章
doi:10.1289/EHP556
更新日期:2017-08-01 00:00:00
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journal_title:Environmental health perspectives
pub_type: 杂志文章,评审
doi:10.1289/ehp.00108s3429
更新日期:2000-06-01 00:00:00
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journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.7646
更新日期:2005-05-01 00:00:00
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pub_type: 杂志文章
doi:10.1289/ehp.11117
更新日期:2008-08-01 00:00:00
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journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.761617
更新日期:1976-08-01 00:00:00