ascorbic-acid and lead-nitrate

Human prostate cancer cells (DU145) implanted into nude mice are deficient in DNase activity. After administration of a vitamin C/vitamin K(3) 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-microm 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.

Topics: Animals; Ascorbic Acid; Cell Death; Coloring Agents; Deoxyribonucleases; Drug Synergism; Enzyme Reactivators; Histocytochemistry; Humans; Lead; Male; Methyl Green; Mice; Mice, Nude; Microscopy, Electron; Nitrates; Prostatic Neoplasms; Vitamin K; Xenograft Model Antitumor Assays

The identification of desmutagens and bioantimutagens in plants has prompted the search for additional plant extracts capable of modifying adverse cellular effects of environmental toxicants. The protective action of crude extracts of Phyllanthus emblica fruits (PFE) against lead (Pb) and aluminium (Al)-induced sister chromatid exchanges (SCEs) was studied in bone marrow cells of Mus musculus. The modifying effect of the crude extract was compared with that of comparable amounts of synthetic ascorbic acid (AA), a major component of the fruits. Oral administration of PFE or AA for 7 consecutive days before exposure of mice to the metals by intraperitoneal injections reduced the frequencies of SCEs induced by both metals. PFE afforded a more pronounced protective effect than AA in counteracting the genotoxicity induced by both Al and Pb: This difference was significant with Pb. The higher protection afforded by PFE may be attributed to the interaction of AA with other natural ingredients present in the crude fruit extract.

Topics: Alum Compounds; Analysis of Variance; Animals; Antimutagenic Agents; Ascorbic Acid; Bone Marrow; Bone Marrow Cells; Dose-Response Relationship, Drug; Fruit; Lead; Male; Metals; Mice; Mutagens; Nitrates; Plant Extracts; Plants, Medicinal; Sister Chromatid Exchange

Topics: Adrenal Cortex; Animals; Ascorbic Acid; Corticosterone; Lead; Male; Nitrates; Organ Size; Rats; Restraint, Physical; Stress, Psychological