Document Detail


Melphalan-induced mutagenesis in an SV40-based shuttle vector: predominance of A.T----T.A transversions.
MedLine Citation:
PMID:  2174727     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The base and sequence specificity of mutagenesis by the carcinogenic antitumor agent melphalan (L-phenylalanine mustard) was examined by in vitro treatment of the plasmid pZ189 followed by replication in human 293 cells, rescue in bacteria, and sequence analysis of mutations in the supF gene. Melphalan was strongly mutagenic in this assay. The induced mutations were predominantly base substitutions, with a minor component of small deletions (3-80 base pairs). Surprisingly, A.T----T.A transversions were by far the most frequent substitutions, suggesting that modifications of adenine may play a major role in mutagenesis. More than half the substitutions were clustered in a C-T-A-A sequence in the anticodon loop. No base substitutions were detected at G-N-C sequences, which are thought to be potential sites of DNA interstrand cross-links. The results raise the possibility that the cytotoxic and mutagenic effects of melphalan may be separable.
Authors:
P Wang; R A Bennett; L F Povirk
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Cancer research     Volume:  50     ISSN:  0008-5472     ISO Abbreviation:  Cancer Res.     Publication Date:  1990 Dec 
Date Detail:
Created Date:  1991-01-22     Completed Date:  1991-01-22     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  2984705R     Medline TA:  Cancer Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  7527-31     Citation Subset:  IM    
Affiliation:
Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298.
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MeSH Terms
Descriptor/Qualifier:
Base Sequence
DNA / drug effects
Dose-Response Relationship, Drug
Genetic Vectors / drug effects*
Humans
Melphalan / pharmacology*
Molecular Sequence Data
Mutagenesis / drug effects*
Simian virus 40*
Transfection
Grant Support
ID/Acronym/Agency:
CA40615/CA/NCI NIH HHS; ES07087/ES/NIEHS NIH HHS
Chemical
Reg. No./Substance:
148-82-3/Melphalan; 9007-49-2/DNA

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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