Activation of human long interspersed nuclear element 1 retrotransposition by benzo(a)pyrene, an ubiquitous environmental carcinogen.

2.50
Hdl Handle:
http://hdl.handle.net/10146/65254
Title:
Activation of human long interspersed nuclear element 1 retrotransposition by benzo(a)pyrene, an ubiquitous environmental carcinogen.
Authors:
Stribinskis, Vilius; Ramos, Kenneth S.
Abstract:
Long interspersed nuclear elements [LINE-1 (L1)] are abundant retrotransposons in mammalian genomes that remain silent under most conditions. Cellular stress signals activate L1, but the molecular mechanisms controlling L1 activation remain unclear. Evidence is presented here that benzo(a)pyrene (BaP), an environmental hydrocarbon metabolized by mammalian cytochrome P450s to reactive carcinogenic intermediates, increases L1 retrotransposition in HeLa cells. Increased retrotransposition is mediated by up-regulation of L1 RNA levels, increased L1 cDNA synthesis, and stable genomic integration. Activation of L1 is dependent on the ability of BaP to cause DNA damage because it is absent in HeLa cells challenged with nongenotoxic hydrocarbon carcinogens. Thus, the mutations and genomic instability observed in human populations exposed to genotoxic environmental hydrocarbons may involve epigenetic activation of mobile elements dispersed throughout the human genome.
Citation:
Cancer Res. 2006, 66 (5):2616-2620
Journal:
Cancer research
Issue Date:
1-Mar-2006
URI:
http://hdl.handle.net/10146/65254
DOI:
10.1158/0008-5472.CAN-05-3478
PubMed ID:
16510580
Additional Links:
http://cancerres.aacrjournals.org/cgi/content/full/66/5/2616
Type:
Article
Language:
en
Description:
KEYWORDS CLASSIFICATION: biosynthesis;Benzo(a)pyrene;Biology;Carcinogens;drug effects;DNA,Complementary;genetics;Hela Cells;Humans;Long Interspersed Nucleotide Elements;mechanisms of carcinogenesis;Molecular Biology;Research;Rna;toxicity;Transfection;Up-Regulation.
ISSN:
0008-5472
Appears in Collections:
Articles with annotation

Full metadata record

DC FieldValue Language
dc.contributor.authorStribinskis, Vilius-
dc.contributor.authorRamos, Kenneth S.-
dc.date.accessioned2009-04-17T12:15:03Z-
dc.date.available2009-04-17T12:15:03Z-
dc.date.issued2006-03-01-
dc.identifier.citationCancer Res. 2006, 66 (5):2616-2620en
dc.identifier.issn0008-5472-
dc.identifier.pmid16510580-
dc.identifier.doi10.1158/0008-5472.CAN-05-3478-
dc.identifier.urihttp://hdl.handle.net/10146/65254-
dc.descriptionKEYWORDS CLASSIFICATION: biosynthesis;Benzo(a)pyrene;Biology;Carcinogens;drug effects;DNA,Complementary;genetics;Hela Cells;Humans;Long Interspersed Nucleotide Elements;mechanisms of carcinogenesis;Molecular Biology;Research;Rna;toxicity;Transfection;Up-Regulation.en
dc.description.abstractLong interspersed nuclear elements [LINE-1 (L1)] are abundant retrotransposons in mammalian genomes that remain silent under most conditions. Cellular stress signals activate L1, but the molecular mechanisms controlling L1 activation remain unclear. Evidence is presented here that benzo(a)pyrene (BaP), an environmental hydrocarbon metabolized by mammalian cytochrome P450s to reactive carcinogenic intermediates, increases L1 retrotransposition in HeLa cells. Increased retrotransposition is mediated by up-regulation of L1 RNA levels, increased L1 cDNA synthesis, and stable genomic integration. Activation of L1 is dependent on the ability of BaP to cause DNA damage because it is absent in HeLa cells challenged with nongenotoxic hydrocarbon carcinogens. Thus, the mutations and genomic instability observed in human populations exposed to genotoxic environmental hydrocarbons may involve epigenetic activation of mobile elements dispersed throughout the human genome.en
dc.language.isoenen
dc.relation.urlhttp://cancerres.aacrjournals.org/cgi/content/full/66/5/2616en
dc.subject.meshBenzo(a)pyrene-
dc.subject.meshCarcinogens-
dc.subject.meshDNA, Complementary-
dc.subject.meshHela Cells-
dc.subject.meshHumans-
dc.subject.meshLong Interspersed Nucleotide Elements-
dc.subject.meshRNA-
dc.subject.meshTransfection-
dc.subject.meshUp-Regulation-
dc.titleActivation of human long interspersed nuclear element 1 retrotransposition by benzo(a)pyrene, an ubiquitous environmental carcinogen.en
dc.typeArticleen
dc.identifier.journalCancer researchen

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