Cancer destruction in vivo through disrupted energy metabolism. Part I. The endogenous mechanism of self-destruction within the malignant cell, and the roles of endotoxin, certain hormones and drugs, and active oxygen in causing cellular injury and death.
Autoxidative cellular injury arises when an intact endogenous mechanism present in cells is triggered by a range of specific stimuli, including endotoxin, stress hormones, hydralazine, L-isoproterenol and certain phenothiazines. The overall changes involve oxygen activation, lipid peroxidation, and the generation of substances which disrupt mitochondrial energy production by uncoupling oxidative phosphorylation. Magnetic resonance spectroscopy has revealed that falls in high-energy phosphate are commonly seen following a variety of therapeutic procedures, including radiation and treatment with cytotoxic agents. Sometimes the energy status of a tumor improves in response to therapy; in these instances tumor regression is due to programmed cell death, termed apoptosis. In the first part of this review the roles played in the development of autoxidative cellular injury by oxygen and its active forms, an endogenous peroxidisable substrate, and an oxygenase are considered and discussed.
Jones
G R
GR
Department of Biochemistry, University of Surrey, Guildford, U.K.
D000818:Animals; D016923:Cell Death / Q000187:drug effects*; D004731:Endotoxins / Q000502:physiology*; D004734:Energy Metabolism / Q000187:drug effects*; D005609:Free Radicals; D006728:Hormones / Q000502:physiology*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D010100:Oxygen / Q000633:toxicity*
D004731:Endotoxins; D005609:Free Radicals; D006728:Hormones; D010100:Oxygen