Change search
ReferencesLink to record
Permanent link

Direct link
DNA repair and replication influence the number of mutations per adduct of polycyclic aromatic hydrocarbons in mammalian cells
Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology.
Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology.
Show others and affiliations
2011 (English)In: DNA Repair, ISSN 1568-7864, E-ISSN 1568-7856, Vol. 10, no 8, 877-886 p.Article in journal (Refereed) Published
Abstract [en]

Polycyclic aromatic hydrocarbons (PAH) are an important class of environmental contaminants many of which require metabolic activation to DNA-reactive bay or fjord region diolepoxides (DE) in order to exert their mutagenic and carcinogenic effects. In this study, the mutagenicity of the bay region diolepoxides (+)-anti-7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE) and ()-anti-1,2-dihydroxy-3,4-epoxy-1,2,3,4-tetrahydrodibenzo[a,h]anthracene (DBADE) and the fjord region diolepoxides ()-anti-11,12-dihydroxy-13,14-epoxy-11,12,13,14-tetrahydrodibenzo[a,l]-pyrene (DBPDE) and (+/-)-anti-3,4-dihydroxy-1,2-epoxy-1,2,3,4-tetrahydrobenzo[c]-phenanthrene (BPhDE) was compared in nucleotide excision repair (NER) proficient and deficient hamster cell lines. The (32)P-postlabelling assay was applied to analyze DNA adduct levels and the Hprt gene mutation assay for monitoring mutations. Previously, we found that the mutagenicity per adduct was four times higher for DBPDE compared to BPDE in NER proficient cells. In these same cells, the mutagenicity of DBADE and BPhDE adducts was now found to be significantly lower compared to that of BPDE. In NER deficient cells the highest mutagenicity per adduct was found for BPDE and there was a tenfold and fivefold difference when comparing the BPDE data with the DBADE and BPhDE data, respectively. In order to investigate to what extent the mutagenicity of the different adducts in NER proficient cells was influenced by repair or replication bypass, we measured the overall NER incision rate, the rate of adduct removal, the rate of replication bypass and the frequency of induced recombination in the Hprt gene. Since NER turned out to be an important pathway for the yield of mutations, we further analyzed the role of transcription coupled NER versus global genome NER. However, our data demonstrate that neither of these pathways seems to be the sole factor determining the mutation frequency of the four PAH-DE and that the differences in the repair efficiency of these compounds could not be related to the presence of a bay or fjord region in the parent PAH.

Place, publisher, year, edition, pages
2011. Vol. 10, no 8, 877-886 p.
Keyword [en]
Polycyclic aromatic hydrocarbons, Nucleotide excision repair, DNA adducts, Replication bypass, Mutations
National Category
Chemical Sciences
URN: urn:nbn:se:su:diva-68317DOI: 10.1016/j.dnarep.2011.06.002ISI: 000294033800010OAI: diva2:477399
authorCount :12Available from: 2012-01-13 Created: 2012-01-03 Last updated: 2012-01-13Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full text

Search in DiVA

By author/editor
Lagerqvist, AnneHåkansson, DanielTörnqvist, MargaretaErixon, KlausJenssen, Dag
By organisation
Department of Genetics, Microbiology and ToxicologyDepartment of Materials and Environmental Chemistry (MMK)
In the same journal
DNA Repair
Chemical Sciences

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 235 hits
ReferencesLink to record
Permanent link

Direct link