Frameshift mutations produced by 9-aminoacridine in wild-type, uvrA and recA strains of Escherichia coli; specificity within a hotspot.
The endogenous tonB gene of Escherichia coli was used as a target for 9-aminoacridine-induced mutations that were identified in recA(-) and uvrA(-) cells. The cytotoxicity of 9-aminoacridine was enhanced in the uvrA and recA strains compared to the wild-type strain, and the mutagenicity of 9-aminoacridine in the uvrA and recA strains was similar to that in the wild type. For all three strains, the most common mutations were minus frameshifts in repetitive G:C base-pairs followed by minus frameshifts in nonrepetitive G:C base-pairs. 9-aminoacridine-induced minus frameshifts in the wild-type strain were distributed with several hot and warm spots. These sites were also hot and warm spots for minus frameshifts in the recA and uvrA stains. Furthermore, they were hot and warm sites in a 9-aminoacridine-treated strain carrying the target tonB gene oriented in the opposite direction. 9-Aminoacridine is known to interact with DNA to form intercalations which are involved in minus frameshift mutagenesis. In this study, we therefore argue that 1) 9-aminoacridine can induce bulky DNA lesions which are excised by nucleotide excision repair and not involved in mutagenesis, 2) the presence or absence of a recA-dependent repair pathway does not influence the mutagenic effect of 9-aminoacridine, and 3) both leading strand and lagging strand replication equally produce minus frameshifts, therefore gene orientation is not an important determinant of the formation of hot and warm spots by 9-aminoacridine.
Acharya
Niranjan
N
Graduate School of Life Sciences, Tohoku University, Sendai, Japan.
Abu-Nasr
Nagla Fathi
NF
Kawaguchi
Genta
G
Imai
Masaru
M
Yamamoto
Kazuo
K
D000585:Aminacrine / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004926:Escherichia coli / Q000502:physiology* / Q000528:radiation effects*; D016368:Frameshift Mutation / Q000187:drug effects* / Q000528:radiation effects*; D011836:Radiation Tolerance / Q000502:physiology; D011938:Rec A Recombinases / Q000378:metabolism*; D014466:Ultraviolet Rays
D000585:Aminacrine; D011938:Rec A Recombinases