Effects of ascorbate ions on intracellular fluorescein emission polarization spectra in cancer and normal proliferating cells.
Ascorbate ions induced a polarization peak in the intracellular fluorescein fluorescence polarization spectra of asynchronous populations of a variety of cancer cell types from human and animal biopsy material or in cells grown in vivo and/or in vitro. The appearance of this polarization peak at 510 nm on excitation at 470 nm (P510 peak) indicates the transition of mitochondria from the condensed (active) into orthodox (resting) conformation. In contrast, no effects of ascorbate ions were observed in the polarization spectra of various normal cell lines. This apparent differential response seems to be caused by the effects of ascorbate ions on several steps of the altered energy metabolism in cancer cells. It appeared not to be due to a defective mechanism responsible for the conformational changes in the mitochondria. In YMDR cells resistant to the antitumor drug methylene-dimethanesulphonate (MDMS), HeLa cells pretreated with colcemid, and YMDS cells pretreated with cytochalasin B, the transition of mitochondria into orthodox conformation could not be induced by ascorbate ions. Thus, it is possible that tumors also pretreated with other drugs become resistant to growth inhibitory effects of ascorbate ions. Induction of the fluorescein emission polarization peak at 510 nm in cells from biopsies or from in vitro-induced malignancies could be used as an additional criterion for malignant transformation.
D019297:2,4-Dinitrophenol; D001205:Ascorbic Acid / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology; D002460:Cell Line; D000242:Cyclic AMP / Q000494:pharmacology; D003571:Cytochalasin B / Q000494:pharmacology; D003703:Demecolcine / Q000494:pharmacology; D004140:Dinitrophenols / Q000494:pharmacology; D004734:Energy Metabolism; D005454:Fluorescence Polarization; D006019:Glycolysis / Q000187:drug effects; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007399:Interphase; D008741:Methyl Methanesulfonate / Q000031:analogs & derivatives / Q000494:pharmacology; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism*
D004140:Dinitrophenols; C002538:methylene dimethanesulfonate; D003571:Cytochalasin B; D008741:Methyl Methanesulfonate; D000242:Cyclic AMP; D001205:Ascorbic Acid; D019297:2,4-Dinitrophenol; D002118:Calcium; D003703:Demecolcine