In vivo reactivation of DNases in implanted human prostate tumors after administration of a vitamin C/K-3 combination

Human prostate cancer cells (DU145) implanted into nude mice are deficient in DNase activity. After administration of a vitamin C/vitamin K-3 combinat ion, both alkaline DNase (DNase I) and acid DNase (DNase II) activities wer e detected in cryosections with a histochemical lead nitrate technique. Alk aline DNase activity appeared 1 hr after vitamin administration, decreased slightly until 2 hr, and disappeared by 8 hr after treatment. Acid DNase ac tivity appeared 2 hr after vitamin administration, reached its highest leve ls between 4 and 8 hr, and maintained its activity 24 hr after treatment. M ethyl green staining indicated that DNase expression was accompanied by a d ecrease in DNA content of the tumor cells. Microscopic examination of 1-mum sections of the tumors indicated that DNase reactivation and the subsequen t degradation of DNA induced multiple forms of tumor cell death, including apoptosis and necrosis. The primary form of vitamin-induced tumor cell deat h was autoschizis, which is characterized by membrane damage and the progre ssive loss of cytoplasm through a series of self-excisions. These self-exci sions typically continue until the perikaryon consists of an apparently int act nucleus surrounded by a thin rim of cytoplasm that contains damaged org anelles.