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 fragmenta tion. No DNA fragmentation of the cells was induced-by 2,2-bis(3-amino propyl)-4,4'-bithiazole, which has little cleaving activity toward pla smid DNA. Analysis of fragmented DNA from thymocytes treated with 2,2- bis(2-aminoethyl)-4,4'-bithiazole by agarose gel electrophoresis revea led that the compound produced 50 kbp DNA fragments and caused internu cleosomal DNA fragmentation. In addition, the confocal microscopic ima ges of thymocytes treated with the compound showed condensation of chr omatin. These results indicate that bithiazole derivative induces thym ocyte apoptosis with the biochemical and morphological characteristics through triggerring DNA scission.