title: Mutagenic activities of azido analogues of amsacrine and other 9-anilinoacridines in Salmonella typhimurium and their enhancement by photoirradiation.
abstract: Analogues of amsacrine and other 9-anilinoacridines, bearing azide groups at various positions, were tested for their mutagenic activity in five strains of Salmonella typhimurium, both before and after photoirradiation. Azido substitution at the 2- or 3-position of the acridine or the 1'-position of the aniline led to compounds which were active frameshift mutagens, as detected in strain TA1537. Photoirradiation enhanced both the mutagenicity and the cytotoxicity of the azido compounds. Analogues bearing two azido groups at either the 2,6- or 3,6-positions were less strongly mutagenic in the dark, and light activation led to a toxic but only weakly mutagenic product. The effects of photoirradiation were decreased by aniline ring substitution, and were essentially eliminated by additional methyl substitution in the acridine ring. Comparison of events in TA1537 and TA98 suggested that photoirradiation of the 2- or 3-azido compounds gave a product which was capable of forming covalent bonds with DNA. The azide-containing analogues readily formed single strand DNA breaks on irradiation in the presence of DNA, but the efficiency of this reaction varied considerably.
authors.affiliation: Department of Microbiology, School of Pharmaceutical Science, University of Shizuoka, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Iwamoto
authors.forename: L R
authors.initials: LR
authors.lastname: Ferguson
authors.forename: H B
authors.initials: HB
authors.lastname: Pogai
authors.forename: T
authors.initials: T
authors.lastname: Uzuhashi
authors.forename: A
authors.initials: A
authors.lastname: Kurita
authors.forename: Y
authors.initials: Y
authors.lastname: Yangihara
authors.forename: W A
authors.initials: WA
authors.lastname: Denny
mesh_terms: D000677:Amsacrine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000633:toxicity*; D004249:DNA Damage; D004587:Electrophoresis, Agar Gel; D016368:Frameshift Mutation; D008027:Light; D009153:Mutagens / Q000737:chemistry / Q000633:toxicity*; D010777:Photochemistry; D010957:Plasmids; D012486:Salmonella typhimurium / Q000187:drug effects
chemical_list: D009153:Mutagens; D000677:Amsacrine; C022202:9-anilinoacridine