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Journal of Histochemistry and Cytochemistry, Vol. 49, 109-120, January 2001, Copyright © 2001, The Histochemical Society, Inc.

ARTICLE

In Vivo Reactivation of DNases in Implanted Human Prostate Tumors After Administration of a Vitamin C/K3 Combination

Henryk S. Tapera, James M. Jamisonb, Jacques Gilloteauxc, Carley A. Gwinb, Timothy Gordonb, and Jack L. Summersb
a Laboratoire de Pharmacologie Toxicologique et Cancérologique, Faculté de Médecine, Université Catholique de Louvain, Brussels-Woluwé, Belgium
b Department of Urology, Summa Health System/Northeastern Ohio Universities College of Medicine, Rootstown, Ohio
c Department of Anatomy, Lake Erie College of Osteopathic Medicine, Erie, Pennsylvania

Correspondence to: James M. Jamison, Dept. of Urology, Northeastern Ohio Universities College of Medicine, 4209 State Route 44, PO Box 95, Rootstown, Ohio 44272-0095. E-mail: jmj@neoucom.edu

Human prostate cancer cells (DU145) implanted into nude mice are deficient in DNase activity. After administration of a vitamin C/vitamin K3 combination, both alkaline DNase (DNase I) and acid DNase (DNase II) activities were detected in cryosections with a histochemical lead nitrate technique. Alkaline DNase activity appeared 1 hr after vitamin administration, decreased slightly until 2 hr, and disappeared by 8 hr after treatment. Acid DNase activity appeared 2 hr after vitamin administration, reached its highest levels between 4 and 8 hr, and maintained its activity 24 hr after treatment. Methyl green staining indicated that DNase expression was accompanied by a decrease in DNA content of the tumor cells. Microscopic examination of 1-µm sections of the tumors indicated that DNase reactivation and the subsequent degradation of DNA induced multiple forms of tumor cell death, including apoptosis and necrosis. The primary form of vitamin-induced tumor cell death was autoschizis, which is characterized by membrane damage and the progressive loss of cytoplasm through a series of self-excisions. These self-excisions typically continue until the perikaryon consists of an apparently intact nucleus surrounded by a thin rim of cytoplasm that contains damaged organelles. (J Histochem Cytochem 49:109–119, 2001)

Key Words: vitamin C, vitamin K3, DNase, prostate cancer, necrobiology, cancer cell death


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