Thymocyte apoptosis induced by various compounds including YO-2 is accompanied by a change in chromatin structure.

To elucidate the role of chromatin structure in DNA fragmentation during apoptosis, we have examined whether chromatin structural change is observed after treatment with proapoptotic compounds. Analysis of the circular dichroism (CD) spectrum of the soluble chromatin from dexamethasone-treated thymocytes revealed a decrease in alpha-helical content. Mifepristone, an antagonist of glucocorticoid receptor, prevented both the change in chromatin structure and DNA fragmentation induced by dexamethasone. The effect of YO-2 [trans-4-aminomethylcyclohexanecarbonyl-l-(O-picolyl)tyrosine-n-octylamide], which possesses proapoptotic action, on chromatin structure was also examined. Judging from the CD spectrum of the soluble chromatin from YO-2-treated thymocytes, the structure was changed by this compound as well as by dexamethasone. A decrease in alpha-helical content was also observed in cells treated with etoposide, which is used clinically as an anticancer agent. These results suggest that the change in chromatin structure is likely to be an important process in DNA fragmentation of cells undergoing apoptosis.