---------------------------------------------------------------------------- ---------------------------------------------------------------------------- The Free-Radical Fallacy about Ionizing Radiation: Demonstration That a Popular Claim Is Senseless By John W. Gofman, M.D., Ph.D., September 1997 ---------------------------------------------------------------------------- ---------------------------------------------------------------------------- * Part 1 -- The Free-Radical Fallacy: "Just Living" Hurts DNA Much More than Ionizing Radiation * Part 2 -- The Relative Frequency of DNA Damage-Events * Part 3 -- Reality-Check for the "Same-Nature" Assumption * Part 4 -- The Unique Power of Ionizing Radiation [Polly wants to express a divergent view to tonight's channel 5 editorial] ------------------------------------------------------------------ Part 1 * The Free-Radical Fallacy: "Just Living" Hurts DNA Much More than Ionizing Radiation 1a * In some peer-review journals and various interviews in the media, what we call the Free-Radical[1] Fallacy has been employed in an effort to deny the menace of low-dose ionizing radiation. Here, we will demonstrate why it is a fallacy. 1b * There is no doubt that routine metabolic chemistry in each cell produces legions of free-radicals every hour, in the process of "just living." And there is no doubt that exposure to ionizing radiation produces some EXTRA free-radicals in irradiated cells. And so radiation scientists such as Dr. Daniel Billen (1990) have tried to argue that low-doses of ionizing radiation must be inconsequential BECAUSE they add so few free-radicals to a cell, by comparison with the number of free-radicals naturally in each cell anyway. 1c * The hidden (and false) assumptions in such reasoning are (1) that the nature of damage done by ionizing radiation is the same as the nature of damage done by routine metabolic free-radicals, and (2) that damage therefore can be compared by comparing the relative numbers of free-radicals. The erroneous "same-nature" assumption is at the heart of the Free-Radical Refrain, and has been disseminated by statements like "We are irradiating ourselves by living" (Dr. Bruce Ames 1994, p.18; Ames 1995, p.5259). 1d * Using numbers from Dr. Billen's own presentation, plus a reality-check with actual observations, we can demonstrate that the nature of damage from ionizing radiation CANNOT POSSIBLY BE THE SAME AS the nature of the damage from routine metabolic free-radicals. We have not seen this demonstration elsewhere, but perhaps someone else has put it forth, too. We use nothing but simple multiplication and division (Part 3). ------------------------------------------------------------------ Part 2 * The Relative Frequency of DNA Damage-Events 2a * Billen (1990, p.242) cites various mainstream sources for two estimates in his free-radical argument: (1) "Approximately 10,000 measurable DNA modification events occur per hour in each mammalian cell due to intrinsic causes," and (2) "About 100 (or fewer) measurable DNA alterations occur per centi-Gray of low-LET radiation per mammalian cell." These two values are made comparable in Part 2d, below. 2b * The goodness of both estimates, above, will surely improve a great deal with future methods of measurement, but neither Billen's argument nor its refutation depends on precision in these two values. Billen's reference to "low-LET" radiation includes x-ray, beta, and gamma radiations. 2c * Billen states his conclusion (p.242): "Therefore, every HOUR, human and other mammalian cells undergo at least 50-100 times as much spontaneous or natural DNA damage as would result from exposure to 1 centi-Gray of ionizing radiation." Centi-Gray and "rad" are two names for the same amount of radiation exposure. How much is one rad of exposure? 2d * On the average, it takes about 10 years for a person to accumulate one rad of whole-body exposure from natural background radiation. So Billen's numbers mean that the ratio of damage-events PER UNIT OF TIME (per hour, or per day, or per year) may be as large as 8.8 million endogenous damage-events for each damage-event due to natural background radiation. A very large difference ... but is it meaningful? 2e * The estimates presented by Billen of "DNA modifications" and "DNA alterations" are estimated numbers PRIOR to repair-work by the cell. Here (and elsewhere in the literature), the term "damage-events" is preferred, to signal that the event is not necessarily an unrepairable PERMANENT mutation of the DNA. 2f * Billen's arithmetic is correct, but a reality-check is needed for his assumption that the nature of DNA damage-events is the same from routine cellular metabolism and from ionizing radiation. ------------------------------------------------------------------ Part 3 * Reality-Check for the "Same-Nature" Assumption 3a * According to Billen, a rad (centi-Gray) causes about 100 or fewer measurable DNA damage-events per cell. 3b * According to Billen, the number of comparable damage-events from intrinsic causes per cell, every HOUR, is 50 to 100 times higher, which means 5,000 to 10,000 damage-events every hour from intrinsic causes, per cell. (Bruce Ames 1995, p.5259, provides an estimate per DAY, not per hour: "The number of oxidative hits to DNA per cell per day is estimated to be about 100,000 in the rat and roughly ten times fewer in the human." We will include this estimate in Point 3e.) 3c * It follows from Billen that per DAY, the DNA damage-events per cell from endogenous causes are either: ( 5,000 events/hr) x (24 hr/day) = 120,000 events/day, or: (10,000 events/hr) x (24 hr/day) = 240,000 events/day ... in each cell. 3d * And something else follows from Billen's assumption that there is no important difference between the endogenous and the radiation-induced damage-events. If correct, then the DNA-based consequences from a radiation dose which delivers 120,000 or 240,000 damage-events each day, per cell, should be the same as from 120,000 or 240,000 such events per cell each day, from endogenous sources. 3e * The whole-body radiation dose per day required (by Billen's numbers) to deliver 120,000 to 240,000 such DNA damage-events per cell, each day, would be either: (120,000 events) x (1 rad/100 events) = 1,200 rads, or: (240,000 events) x (1 rad/100 events) = 2,400 rads. And: If we substitute Ames' figure (from Point 3b), we would calculate (10,000 events) x (1 rad/100 events) = 100 whole-body rads per day to deliver DNA damage equivalent to daily damage from intrinsic causes. Bottom Line of the Reality-Check 3f * If there were equivalance between DNA damage by free radicals from normal, intrinsic processes and DNA damage from ionizing radiation, then whole-body doses of 100 rads to 2,400 rads per day EVERY day would be easily tolerated. Instead, such doses are promptly lethal. 3g * For half the humans exposed, promptly-lethal doses are estimated by the radiation community at 300 whole-body internal-organ rads accumulated in one week or less (or 420 such rads within a month). 3h * There is an additional observation worth noting. The background rate of cancer (a disease widely acknowledged to be DNA-related) is doubled by extra radiation doses of a few hundred whole-body rads, or fewer, of accumulated exposure. According to Billen (Point 3a), 300 rads cause about 30,000 or fewer DNA damage-events per cell --- a number far exceeded in a single day by intrinsic processes (Point 3b). If DNA damage from intrinsic causes and from low-LET ionizing radiation were equivalent, it is hard to see how anyone could escape having MULTIPLE clinical cancers from intrinsic processes. 3i * From these two reality-based observations (acute lethal doses and doubling-doses for radiation-induced cancer), we have demonstrated that the nature of damage caused by ionizing radiation CANNOT POSSIBLY BE THE SAME as it is from normal metabolic processes and oxidative damage. Without an equivalence, the Billen argument and its variations collapse. The Free-Radical Refrain is just a Free-Radical Fallacy. ------------------------------------------------------------------ Part 4 * The Unique Power of Ionizing Radiation 4a * The difference between free-radical damage from routine metabolism and from ionizing radiation almost surely lies in REPAIRABILITY. If DNA damage is perfectly repaired by a cell, such damage has no health consequences. It is inconsequential. The consequences arise only from injuries which are non-repairable or mis-repaired. 4b * The demonstration in Part 3 supports other evidence (and vice versa) that ionizing radiation can induce the special kinds of complex DNA damage which CANNOT BE PERFECTLY REPAIRED. A leading figure in this research is John F. Ward; see Reference List. 4c * The power of ionizing radiation to induce the complex injuries is not in dispute. Billen himself appears to acknowledge it, but then to ignore it (Billen 1991, p.388). 4d * The power of ionizing radiation to induce particularly complex and unrepairable genetic injuries is surely related to a UNIQUE PROPERTY of this agent. Ionizing radiation instantly unloads biologically abnormal amounts of energy at random in an irradiated cell. Biochemical reactions in a cell generally involve net energy-transfers in the ballpark of 10 electron-volts and below. By contrast, Ward reports (1988, p.103) that the average energy-deposit from low-LET ionizing radiation is thought to be about 60 electron-volts, all within an area having a diameter of only 4 nanometers. (The diameter of the DNA double-helix is 2 nanometers). In other words, ionizing radiation produces violent energy-transfers of a type simply absent in a cell's natural biochemistry. 4e * Because of its unique property, ionizing radiation is a unique menace to our DNA and chromosomes. This fact needs wide recognition, as mankind learns that FAR more health problems are mutation-based than anyone could prove 15 years ago. # # # # # References: * Ames 1994 (Bruce N.), interviewed by Russell Schoch in California Monthly (Univ. of California, Berkeley), June 1994, at page 18. * Ames 1995 (Bruce N.), "The Causes and Prevention of Cancer," Proceedings Natl Acad Sci USA Vol.92: 5258-5265. * Billen 1990 (Daniel), (commentary) "Spontaneous DNA Damage and Its Significance for the `Negligible Dose' Controversy in Radiation Protection," Radiation Research Vol.124: 242-245. * Billen 1991 (Daniel), (letter) "Response to Comments of K.F. Baverstock and J.F. Ward," Radiation Research Vol.126: 388-389. * Ward 1985 (John F.), "Mammalian Cells Are Not Killed by DNA Single-Strand Breaks Caused by Hydroxyl Radicals from Hydrogen Peroxide," Radiation Research Vol.103: 383-392. * Ward 1988 (John F.), "DNA Damage Produced by Ionizing Radiation in Mammalian Cells: Identities, Mechanisms of Formation, and Reparability," Progress in Nucleic Acid Research & Molecular Biology Vol.35: 95-125. * Ward 1990 (John F.), "The Yield of DNA Double-Strand Breaks Produced Intracellularly by Ionizing Radiation: A Review," International Journal of Radiation Biology Vol.57: 1141-1150. * Ward 1991 (John F.), (letter) "Response to Commentary by D. Billen," Radiation Research Vol.126: 385-387. For more details on the unique action of ionizing radiation, and on the repair-issue, see: * Gofman 1990, Radiation-Induced Cancer from Low-Dose Exposure. 480 pages. Chapter 19 "The Special Interaction of Ionizing Radiation with Living Tissue," and Chapter 20 "Various Radiation Sources: Primary Electron-Tracks per Nucleus per Rad." Book available from CNR ($29.95), and online at . * Gofman 1995, "What Is Factually Wrong with This Belief: `Harm from Low-Dose Radiation Is Just Hypothetical --- Not Proven'." 4 pages. Available from CNR and online at . * Gofman 1996, Preventing Breast Cancer. 422 pages. Chapter 45 "Three Remarkably Similar Reports on the Safe-Dose Fallacy." Book available from CNR ($17), and online at . * Gofman 1996, "Answers to Frequently-Asked-Questions about `Radiation'." 4 pages. Available from CNR and online at . 1. Free-radicals are highly reactive molecules possessing an unpaired electron. In our cells, such radicals can do injury (for instance, oxidative damage) to proteins and other molecules --- including the DNA molecules which encode the human genes. # # # # # Committee for Nuclear Responsibility, Inc. 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