Anticarcinogenesis and Radiation Protection

Inhaltsverzeichnis

1. Frontmatter

2. Free Radical Mechanisms

   1. The Involvement of Free Radicals in Chemical Carcinogenesis

      William A. Pryor

      Abstract

      Cancer is a multi-step process, involving three stages that can be operationally distinguished: initiation, promotion and progression. Initiation involves an irreversible alteration of the cellular DNA that permits the transformation of the cell to a non-malignant state. Promotion produces conditions that allow the initiated cell to become malignant, and progression is the growth of the malignant cell to a tumor.

   2. Autoxidation and Enzymatic Oxidation of Unsaturated Lipids

      Ned A. Porter

      Abstract

      Oxygen may act not only as an oxidant to initiate free radical reactions, but it can also act as a substrate for the propagation of these reactions. The spontaneous reaction of molecular oxygen with radicals is commonly referred to as autoxidation. Autoxidation is responsible for the deterioration of many manufactured plastics and rubber goods. Rancidity and spoilage of foodstuffs is a direct result of the autoxidation of fats, which are most susceptible to air oxidation and present, to a large extent, in virtually all foods.

   3. Electron vs. H-Atom Transfer in Chemical Repair

      Michael G. Simic, Edward P. L. Hunter, Slobodan V. Jovanovic

      Abstract

      Free radicals are generated by ionizing radiations (e.g., X rays, γ rays, electrons, neutrons, and Rn α-particles),¹ and the biological effects they cause are in some ways a consequence of their reactions.² Free radicals may also be generated by other processes and agents and numerous chemicals generate them under physiological conditions. Cancer promoters³ and antineoplastic drugs⁴ cause DNA strand breaks via free radical reactions. Metabolic processes are also perceived as possible sources of free radicals.^5–7 The repair of free radicals and the elimination (or reduction) of their biological effects by radioprotectors (mainly sulfhydryls) is a well-established defense mechanism in biological systems⁸. Although the interaction of anticarcinogens (primarily antioxidants) with free radicals is feasible, this is a poorly understood process.^8,9

   4. Radiation Induced Reactions of Glutathione with Oxygen and their Possible Role in Biological Systems

      M. Tamba, G. Simone, M. Quintiliani

      Abstract

      The reactivity of some thiyl radicals with molecular oxygen were measured and reported much before the intracellular thiols began to arouse the wave of interest that has characterized the last decade or so (1,2). Cellular thiols, almost entirely consisting of glutathione (GSH), are considered at the present time as one of the most important system capable of protecting cells against free radicals formed during oxidative metabolism or from exposure to drugs or ionizing radiation.

   5. Potential Limitation to Hydrogen Atom Donation as a Mechanism of Repair in Chemical Models of Radiation Damage

      J. A. Raleigh, A. F. Fuciarelli, C. R. Kulatunga

      Abstract

      Ionizing radiation can be lethal to mammalian cells. For those cells which are irradiated and survive, irradiation can also be mutagenic or, in the case of cells in animal tissues, carcinogenic. The biological effects of ionizing radiation are generally believed to originate in free radical reactions. In particular, a radical competition model has been proposed to account for the “oxygen effect” on radiation lethality — the so-called “oxygen fixation” hypothesis (Figure 1) (1–5).

   6. Mechanisms of Inactivation of Oxygen Species by Carotenoids

      Norman I. Krinsky

      Abstract

      Although carotenoid pigments have been implicated as anti-carcinogenic compounds for several years, based on both epidemiological evidence (1) as well as experiments in animals (2,3), the exact mechanism whereby this widely distributed class of componds functions is still poorly understood. What appears to be important however, is the fact that many of the effects of carotenoids in vivo and in vitro can be observed with pigments that do not function as precursors of vitamin A (retinol). For example, beta-carotene may exert its biological effects merely by functioning as a precursor of retinal and retinol. On the other hand, there are carotenoid pigments, such as canthaxanthin (4,4’-diketo-beta-carotene) which also exhibit anti-carcinogenic properties and cannot be converted to retinol (Figure 1). Under these circumstances, we must look at the properties of the intact molecules in order to understand their functions.

   7. Inhibition of Autoxidation by Vitamin E and Bilirubin

      Mohammed Al-Sheikhly, Michael G. Simic

      Abstract

      Antioxidants are known to have an anticarcinogenic effect^1,2. Although they are capable of reducing the incidence of tumors induced by chemical carcinogens, their effect on radiation-induced tumors has not been clearly demonstrated^3,4. The mechanism of the anticarcinogenic action of antioxidants is poorly understood, and despite numerous mechanistic studies of autoxidation processes and antioxidants in model systems, detailed reaction mechanisms under physiological conditions are still elusive. However, inhibition of free radical processes may be an important part of this activity.