A novel DNA cleaving agent, 2,2'-bis(2-aminoethyl)-4,4'-bithiazole, induces thymocyte apoptosis.
The incubation of rat immature thymocytes with 2,2-bis(2-aminoethyl)-4,4'-bithiazole, which possesses the cleaving activity toward plasmid DNA in the presence of Co2+, resulted in an increase in DNA fragmentation. No DNA fragmentation of the cells was induced by 2,2-bis(3-aminopropyl)-4,4'-bithiazole, which has little cleaving activity toward plasmid DNA. Analysis of fragmented DNA from thymocytes treated with 2,2-bis(2-aminoethyl)-4,4'-bithiazole by agarose gel electrophoresis revealed that the compound produced 50 kbp DNA fragments and caused internucleosomal DNA fragmentation. In addition, the confocal microscopic images of thymocytes treated with the compound showed condensation of chromatin. These results indicate that bithiazole derivative induces thymocyte apoptosis with the biochemical and morphological characteristics through triggering DNA scission.
Lee
E
E
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kobe-Gakuin University, Japan.
Miyaguchi
F
F
Inoue
M
M
Kariya
K
K
Sasaki
H
H
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002614:Chelating Agents / Q000494:pharmacology*; D053938:DNA Fragmentation; D004278:DNA, Superhelical / Q000378:metabolism*; D004533:Egtazic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D018613:Microscopy, Confocal; D051381:Rats; D017207:Rats, Sprague-Dawley; D013601:T-Lymphocytes / Q000166:cytology*
D002614:Chelating Agents; D004278:DNA, Superhelical; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D004533:Egtazic Acid; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid