Monofunctional adenine N-3 adducts of melphalan: Occurrence at a mutational hotspot sequence and resistance to removal by AlkA protein
✍ Scribed by Kwabena Charles; Gwen B. Bauer; Lawrence F. Povirk
- Book ID
- 101265077
- Publisher
- John Wiley and Sons
- Year
- 1998
- Tongue
- English
- Weight
- 218 KB
- Volume
- 31
- Category
- Article
- ISSN
- 0893-6692
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✦ Synopsis
Previous work showed that a CTAAA sequence in lan with free adenine base. Various spectrometric the supF gene of the shuttle plasmid pZ189 was a analyses of this species were all consistent with its hotspot for mutagenesis by the aromatic nitrogen identification as a monofunctional adenine N-3 admustards melphalan and chlorambucil, and indirect duct of melphalan. There was no evidence for any evidence suggested adenine N-3 adducts as premu-bifunctional adducts involving the labeled adetagenic lesions. In order to characterize the adducts nines. There was little if any release of the adenine formed at this sequence more directly, a substrate N-3 adduct of melphalan by Escherichia coli AlkA was prepared in which the three adjacent adenines protein, under conditions where 3-methyladenine in the CTAAA sequence were 3 H-labeled. Following was quantitatively released. The results support the treatment of this substrate with [ 14 C]melphalan, ther-proposal that monofunctional adenine N-3 adducts molabile adducts were depurinated and analyzed are intermediates in the generation of ArT r TrA by HPLC. Only a single peak bearing both 3 H and and ArT r CrG transversions by aromatic nitrogen 14 C label was detected and it coeluted with the sin-mustards. Environ. Mol. Mutagen. 31:333 -339, gle major adduct formed by the reaction of melpha-1998 ᭧ 1998 Wiley-Liss, Inc.