DNA adducts of aristolochic acid II: total synthesis and site-specific mutagenesis studies in mammalian cells
| Jazyk: | English |
|---|---|
| ISSN: | 1362-4962 0305-1048 |
| Přístupová URL adresa: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8e2099f73790a71d83031c8c44679986 http://europepmc.org/articles/PMC2800210 |
| Rights: | OPEN |
| Přírůstkové číslo: | edsair.doi.dedup.....8e2099f73790a71d83031c8c44679986 |
| Autor: | Yujing Wen, Francis Johnson, Arthur P. Grollman, Masaaki Moriya, Mark Lukin, Charles R. Iden, Radha Bonala, Sivaprasad Attaluri, In-Young Yang |
| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
DNA polymerase
medicine.disease_cause chemistry.chemical_compound DNA Adducts Mice Plasmid Genetics medicine Animals Nucleotide Site-directed mutagenesis Cells Cultured chemistry.chemical_classification biology Mutagenesis Transfection DNA Molecular biology chemistry Biochemistry Oligodeoxyribonucleotides Synthetic Biology and Chemistry biology.protein Mutagenesis Site-Directed Aristolochic Acids Genotoxicity |
| Zdroj: | Nucleic Acids Research |
| ISSN: | 1362-4962 0305-1048 |
| Popis: | Aristolochic acids I and II (AA-I, AA-II) are found in all Aristolochia species. Ingestion of these acids either in the form of herbal remedies or as contaminated wheat flour causes a dose-dependent chronic kidney failure characterized by renal tubulointerstitial fibrosis. In approximately 50% of these cases, the condition is accompanied by an upper urinary tract malignancy. The disease is now termed aristolochic acid nephropathy (AAN). AA-I is largely responsible for the nephrotoxicity while both AA-I and AA-II are genotoxic. DNA adducts derived from AA-I and AA-II have been isolated from renal tissues of patients suffering from AAN. We describe the total synthesis, de novo, of the dA and dG adducts derived from AA-II, their incorporation site-specifically into DNA oligomers and the splicing of these modified oligomers into a plasmid construct followed by transfection into mouse embryonic fibroblasts. Analysis of the plasmid progeny revealed that both adducts blocked replication but were still partly processed by DNA polymerase(s). Although the majority of coding events involved insertion of correct nucleotides, substantial misincorporation of bases also was noted. The dA adduct is significantly more mutagenic than the dG adduct; both adducts give rise, almost exclusively, to misincorporation of dA, which leads to AL-II-dA-->T and AL-II-dG-->T transversions. |
| Databáze: | OpenAIRE |
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