Gene deletion, a mechanism of induced mutation by arabinosyl nucleosides.
9-beta-D-Arabinofuranosyl-2-fluoroadenine (F-ara-A) and 9-beta-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 material. 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.
Huang
P
P
Graduate School of Biomedical Sciences, University of Texas Health Science Center, Houston 77030.
Siciliano
M J
MJ
Plunkett
W
W
D000818:Animals; D015139:Blotting, Southern; D002460:Cell Line; D002872:Chromosome Deletion; D006224:Cricetinae; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics; D009154:Mutation / Q000187:drug effects*; D012333:RNA, Messenger / Q000235:genetics; D014740:Vidarabine / Q000031:analogs & derivatives* / Q000633:toxicity*
D012333:RNA, Messenger; D007041:Hypoxanthine Phosphoribosyltransferase; D014740:Vidarabine; C024352:fludarabine