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KMID : 0043320100330040633
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Archives of Pharmacal Research
2010 Volume.33 No. 4 p.633 ~ p.636
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Mutation Spectra Induced by Adozelesin in the supF Gene of Human XP-A Fibroblasts
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Lee Chong-Soon
Lee Se-Young
Pfeifer Gerd P.
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Abstract
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Adozelesin is a synthetic analog of the antitumor antibiotic, CC-1065, which alkylates N3 of adenine in the minor DNA groove in a sequence-specific manner. Here we tested the mutation spectra induced by adozelesin in the supF gene of human XP-A fibroblasts using a shuttle vector assay. Adozelesin primarily induces mutations via an A → T transversion and a single base insertion. The A → T transversion (43/59) was observed at the adenine alkylation site in the 5’-ATTTA* sequence (A* is the site of alkylation). The single base insertion (5/59) was observed at the 3’-side of the covalently modified adenine in the 5’-CTAAA* sequence. The results of this study suggest that the DNA alkylating sequence of adozelesin influences the type of DNA mutation.
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KEYWORD
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Mutational specificity, Shuttle vector plasmid pSP189, Adozelesin, supF gene, Anticancer drug
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