Abstract
9-β-d-Arabinofuranosyl-2-fluoroadenine (F-ara-A) and 9-β-d-arabinofuranosyladenine (ara-A) are purine nucleoside analogues which are incorporated into nucleic acids. This study demonstrates the mutagenic properties of F-ara-A and ara-A and provides evidence for mechanisms by which the arabinosyl nucleosides induce mutation. At the drug dosages that evoked exponential cell killing, F-ara-A and ara-A caused a significant increase in the number of 6-thioguanine-resistant mutants in Chinese hamster ovary cells. Southern analyses showed that 15 of 16 drug-induced mutants had lost all or part of the HPRT gene, whereas no loss of the gene was found in 4 spontaneous mutants. We conclude that both F-ara-A and ara-A induced mutation predominantly by causing deletion of genetic method. The remarkable frequency of gene deletion among these drug-induced mutations is discussed with respect to possible mechanisms of action of arabinosyl nucleosides in mutational studies.
Original language | English (US) |
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Pages (from-to) | 291-301 |
Number of pages | 11 |
Journal | Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis |
Volume | 210 |
Issue number | 2 |
DOIs | |
State | Published - Feb 1989 |
Keywords
- Gene deletion
- Mutagenicity
- Nucleoside analogues
ASJC Scopus subject areas
- Molecular Biology
- Genetics
- Health, Toxicology and Mutagenesis