Mutation spectra induced by adozelesin in the supF gene of human XP-A fibroblasts.
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.
Lee
Se-Young
SY
School of Biotechnology, Yeungnam University, Gyeongsan, 712-749, Korea.
Pfeifer
Gerd P
GP
Lee
Chong-Soon
CS
D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology*; D001572:Benzofurans; D002461:Cell Line, Transformed; D003509:Cyclohexanecarboxylic Acids / Q000494:pharmacology*; D053138:Cyclohexenes / Q000494:pharmacology*; D000080890:Duocarmycins; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D016153:Genes, Suppressor; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D009154:Mutation; D010957:Plasmids; D012343:RNA, Transfer / Q000235:genetics*
D018906:Antineoplastic Agents, Alkylating; D001572:Benzofurans; D003509:Cyclohexanecarboxylic Acids; D053138:Cyclohexenes; D000080890:Duocarmycins; D007211:Indoles; C096275:supF tRNA; C060090:adozelesin; D012343:RNA, Transfer