X-Radiation and Gamma Radiation: Comments on Their Nomination as Known Human Carcinogens for the Eleventh Report on Carcinogens (RoC) John W. Gofman, M.D., Ph.D.* Professor Emeritus of Molecular and Cell Biology, U.C. Berkeley September 11, 2001 Submitted by Priority Mail to: Dr. C.W. Jameson National Inst. of Environmental Health Sciences (NIEHS) National Toxicology Program (NTP) 79 Alexander Drive, Building 4401, Room 3118 PO Box 12233 Research Triangle Park NC 27709 For the convenience of the NTP, this submission includes a copy of the author's 1999 peer-reviewed monograph, Radiation from Medical Procedures in the Pathogenesis of Cancer and Ischemic Heart Disease: Dose-Response Studies with Physicians per 100,000 Population. * The author's CV is summarized on the two final pages of this submission. Part 1: How Many Citizens Are Exposed to X-Radiation? Part 2: How Big Are X-Ray Doses in Medical Imaging? Tables 1 & 2. Part 3: A Major New Addition to Evidence that X-Rays Are a Known Human Carcinogen. Part 4: The Absence of Any Risk-Free (Safe) Dose-Level of Low LET Radiation. Part 5: Complex Mutations and Genomic Instability in X- and Gamma-Irradiated Cells. References Peer-Review Author's CV Part 1: How Many U.S. Citizens Are Exposed to X-Rrays and Gamma Rays? These comments apply primarily to x-ray exposure received during medical imaging procedures (during diagnosis, during surgery, during placement of catheters, needles). These comments do not address x-rays and gamma rays used at very high doses for cancer therapy because the Report on Carcinogens (RoC) lists causes of cancer, not potential treatments. The number of x-ray imaging procedures performed annually in the USA was and remains poorly documented. For instance, the annual number for 1985-1990 in the USA was estimated to be at least 800 diagnostic x-ray exams per thousand population, excluding dental x-rays (UNSCEAR 1993, Table 6, p.279). That estimate "could be an underestimate by up to 60%" (UNSCEAR 1993, p.229/46). X-ray imaging procedures are hardly limited to older, presumably less radio-sensitive persons. According to NCRP 1989 (at p.19, citing the FDA in 1985), 47% of all x-ray imaging exams were administered to patients below age 45 years. Since 1990, the number of procedures giving the highest doses --- namely fluoroscopy and CT scans --- have increased dramatically. Despite earlier expectations that MRI would replace CT, the use of CT has increased ceaselessly at an estimated rate of about 10% per year "and will continue to increase for the foreseeable future" (Ravenel 2001, p.279). The estimated number in 1998 was about 33 million CT exams (Nickoloff 2001, p.285). The use of fluoroscopy during diagnostic cardiac catheterizations (estimated over 1 million times per year), during cardiac angioplasty (estimated over 700,000 times per year), and during other procedures, also has increased substantially in recent years (Shope 1997, p.i). Fluoroscopy creates the potential for very high, localized x-ray doses (hundreds of centi-Grays or rads), because the x-ray beam stays "on" either continuously or in a pulsed fashion. There can be no doubt that significant numbers of U.S. citizens are exposed every year to medical x-rays for imaging purposes. Moreover, the evidence is overwhelming now that there is no threshold dose (no risk-free dose); please see Part 4. Therefore, every exposure counts, and the consequences (including carcinogenic mutations) accumulate. Part 2: How Big Are X-Ray Doses in Medical Imaging? Tables 1 and 2 The mistaken assumption, that x-ray exposure from medical imaging is negligible, has been very widely embraced. Although the NTP Reports on Carcinogens explicitly exclude any risk-assessments, the NTP has the responsibility to evaluate whether or not exposure to a nominated carcinogen is literally negligible. Part 2 will show that x-ray exposure from medical imaging has been, and continues to be, far from negligible. It is much higher than appreciated. In 1990, the BEIR-5 Committee embraced without critique the 1987 estimate by the National Council on Radiation Protection, that the average annual per capita "effective" dose equivalent from "x-ray diagnosis" was only 0.039 centi-Sievert (cSv) or rem (BEIR 1990, p.18). We have challenged that estimate as non-credible (Gofman 1999, pp.33-38), and have shown the basis for estimating that annual average per capita dose from diagnostic medical x-rays in 1950 may well have been as high as 0.65 centi-Gray or rad (Gofman 1999, pp.609-616). Since 1950, there may be only a little net change. Because x-ray doses were not and still are not measured, this is a question where uncertainty will be permanent. But the immense growth in CT and fluoroscopy since 1975 may well have offset the post-1950 dose-lowering effects of tuberculosis-eradication, the phase-out of pre-delivery pelvimetry, and introduction of faster films and better beam collimation. Patients More Exposed than Nuclear Workers and Japanese A-Bomb Survivors Tables 1 and 2 are located between pages 3 and 4. Table 1 shows why medical patients can readily accumulate doses from x-rays considerably higher than the average annual dose accumulated occupationally by civilian "nuclear workers," who now accumulate less than 0.5 centi-sievert per year, on the average. Table 2 indicates why it is easy for patients to accumulate higher doses to some internal organs than did most survivors of the Hiroshima-Nagasaki bombs --- a comparison which necessarily requires adjustment for the higher mutagenic potency of 90 kVp x-rays than the mutagenic potency of a-bomb gamma rays. Gofman 1999 (pp.46-48) provides a detailed analysis of this point, with many references from the peer-reviewed literature. ------------------------------------------------------------------ Table 1. COMPUTED TOMOGRAPHY (CT) X-RAY EXAMS: Estimated Doses to Patients * CT doses below are merely "ballpark" values. Entrance doses during CT scans are almost never measured. Actual doses --- even from the same equipment for the same patient --- can vary many-fold according to the settings selected for kVp, mAs, pitch, filtration, slice-width, and some other variables. * Real doses in centi-Gray units (cGy) are distinctly different entities from "effective" doses in centi-Sievert units (cSv). Real doses quantify energy per gram of tissue delivered by an x-ray exam to the irradiated sections of the body, whereas "effective" doses are artificial values based on assumptions about risk ("detriment"). The calculated "effective" dose suggests what dose, if given to the entire body, might produce approximately the same amount of risk as would the real dose received by the irradiated sections. Please see additional comments in the text, Part 2. * The centi-Gray (cGy) and the rad are identical units. There are 10 milli-Gray (mGy) per centi-Gray (cGy) or rad. The centi-Sievert (cSv) and rem are interchangeable units. * This table begins with the typical extra "effective" radiation dose from commercial flying in the USA, because medical patients are so often told that their x-ray dose is about the same as the extra radiation from one trip. For CT exams, the table shows that the claim would be very mistaken. The righthand column divides CT "effective" doses by the "effective" dose from a ten-hour airplane flight in the US (0.003 cSv). The lowest ratio is 50, for just one scan. The ratio for one CT "study" involving 2 or 3 scans would be 2 or 3 times higher than the ratios in the righthand column. Please see additional notes below the tabulation. TOPIC TYPE OF DOSE ESTIMATED DOSE SOURCE Eff.Dose: CT/flying Extra radiation "Effective" 0.0003 cSv per UNSCEAR 1993, during commercial dose/hr. And hour. And p.38. airplane flights per 10 hours. 0.003 cSv per within USA. 10 hours. CT scans, Tissue dose 1-3 cSv. Mettler 2000, general. per scan. p.352. CT head scan, Surface dose. 3-7 cGy Nickoloff adult. (rads). 2001, p.285. CT head scan, "Effective" 0.15 cSv. Mettler 2000, 50 to 1. adult. dose. p.352. CT chest, Surface dose. 2-5 cGy (rads). Nickoloff typical. 2001, p.286. CT chest, "Effective" 0.54 cSv. Huda 2000, 180 to 1. typical. dose. p.843. CT chest, Breast: Mean Up to 5 cGy Gray 1998-a, unspecified. glandular (rads). p.63. dose. CT multi-slice of Surface dose. Up to 10-20 Nickoloff heart for cGy. 2001, p.286. calcium score. CT chest Surface dose. 2-4 cGy (rads). Nickoloff angiograph. 2001, p.286. CT chest, cancer Surface dose. 0.2 - 0.4 cGy Nickoloff screening. (rad). 2001, p.286. Electron Beam CT X-ray beam Reduced dose to Nickoloff chest angiography travels from breasts and 2001, p.286. or cardiac back to front chest calcium front. wall. score. "EBCT." CT abdominal, Surface dose. 2-5 cGy (rads). Nickoloff adult. 2001, p.285. Adult. "Effective" 0.39 cSv. Ware 1999, 130 to 1. dose. p.64. Young adult. "Effective" 0.44 cSv. Ware 1999, 147 to 1. dose. p.64. Child. "Effective" 0.61 cSv. Ware 1999, 203 to 1. dose. p.64. CT-fluoroscopy, Range of 20-60 cGy Nickoloff for imaging in typical (rads) per 2001, p.285. biopsies, etc. dose-rates. minute. * The "effective" doses above, for medical procedures, have very probably not been properly adjusted upward yet for the greater mutagenic power per cGy (rad) of 90-120 kVp x-rays, compared with 250 kVp x-rays and a-bomb gamma rays (details in Gofman 1999, pp.46-48). * The "effective" doses above do not yet incorporate the risk of x-ray-induced coronary artery disease (Gofman 1999, Chapters 39-46). * A handy approximation is that, during helical CT scans, the real dose (cGy or rads) at the body's center is approximately half of the surface dose (Nickoloff 2001, p.285). Except for Electron Beam CT (EBCT), the CT procedures above irradiate the body by revolving the x-ray beams fully around the head or torso. * A CT "study" may involve 2 or 3 repeats ("phases") on the same day. Over 90% of abdominal/pelvic CT studies use 2 or more CT scans (Mettler 2000, p.355). The dose from such studies is the sum of single per-scan doses above. ------------------------------------------------------------------ Table 2. FLUOROSCOPIC X-RAYS: Dose-Rates per Minute, and One Estimate for Cardiac Balloon Angioplasty. * Fluoroscopy creates the potential for very high, localized doses (hundreds of centi-Grays or rads), because the x-ray beam stays "on" either continuously or in a pulsed fashion. Dose to patients can be reduced by less "on-time," but reduced time is far from the only option for achieving dramatic dose-reductions. Many additional and demonstrated ways exist to obtain good images during fluoroscopy at much lower doses than the customary doses currently delivered (Gray 1998-b; Koenig 2001-b). * The roentgen (R) is a dose-unit very close to the centi-Gray (cGy) and rad. Sometimes fluoroscopic dose-rates are stated in roentgens (R) per minute. Fluoroscopy, Dose-rate per 2 to 50 cGy FDA 1994, pp.2-3. general. minute, on (rads) per equipment made minute. before 1995. Upper limit can be restricted by choice to 20. Equipment made 2 to 20 cGy Code of Fed. after 1995. (rads) per Regulations: minute. 21 CFR 1020.32 (e) Flu Equip. CT-fluoroscopy, "Typical" 20 to 60 cGy Nickoloff 2001, e.g. for complex dose-rates (rads) per p.285. needle biopsies. delivered per minute. minute. Fluoroscopy Surface dose, 60 cGy (rads) NCRP 1989, p.31. during cardiac estimated per total, per angioplasty. stenosis. stenosis. * Other procedures with long fluoroscopy times: Angioplasty of non-coronary vessels, stent and filter placement, thrombolytic or fibronolytic procedures, percutaneous transhepatic cholangiography, percutaneous nephrostomy, biliary drainage, urinary/biliary stone removal (FDA 1994). * Procedures where localized skin-dose from fluoroscopy is likely to exceed 100 cGy (rads): RF cardiac catheter ablation, vascular embolization, transjugular intra-hepatic portosystemic stent placement, and percutaneous endovascular reconstruction (Shope 1996, p.1199). One exceptional patient accumulated an estimated local skin dose of 2,100 cGy from fluoroscopy during a series of biliary procedures (Shope 1996, p.1197). * When the skin receives very high doses, the organs beneath receive high doses too. Skin injuries begin at accumulated doses of about 200 cGy (rads), and increase in severity with increasing dose (details in Gofman 1996, pp.184-186, and Koenig 2001-a., Table 3). * Because cardiac procedures are so frequent, their rate of x-ray-induced skin injuries appears to be the highest (Koenig 2001-a, Table 1). ------------------------------------------------------------------ The Higher Mutagenic Power of Medical X-Rays than High-Energy Gamma A reasonable estimate at this time is that the cancer-risk per rad or centi-gray is about three times higher from 90 kVp x-rays than from a-bomb gamma rays. Therefore, in risk-assessment, it would be a severe error to assume that results from the a-bomb study apply directly to medical patients. Table 1: The Difference between Real Doses and "Effective" Doses Doses are reported in units of grays or rads. A dose of ionizing radiation is a quantity of energy delivered per gram of tissue. A rad means 100 ergs of energy per gram of tissue. Since there are 100 rads per gray, 1 rad is exactly the same dose as one centi-gray (cGy). The roentgen is a dose-unit roughly equivalent to the rad or cGy. By contrast, the term "effective" before a dose is a big flag which means, "This is not a dose at all; it is an artificial value which estimates relative detriment." The effective dose is an attempt to estimate what dose to the entire body would have caused the same amount of detriment (risk) as the actual exam which irradiated only specific parts of the body (McCullough 2000). Thus, "effective" doses are usually considerably lower than real doses --- as Table 1 shows. The dose-unit is the centi-Sievert (cSv), which is exactly the same as the rem. These units incorporate a crude adjustment for the different mutagenic potency of x and gamma (low LET) vs. alpha (high LET) radiation. "Effective" doses are necessarily much less credible than real doses, because "effective" doses incorporate a long series of estimates and assumptions about "tissue weighting factors," which attempt (despite woefully inadequate evidence) to assess the attributable probability of fatal cancer in different organs, of the additional detriment from non-fatal cancer and hereditary disorders, and of the different latency periods for cancers of different kinds. By contrast, a real dose is an estimate or measurement of something objective: Energy delivered per gram of tissue. McCullough emphasizes that "It is important to recall that these [effective doses] are estimates, based on many assumptions, and are not directly applicable to any one individual . . . These values, although not intended to describe the dose to an individual, can be used as a relative measure of stochastic injury (e.g., cancer induction or genetic effects)" (McCullough 2000, p.835). Table 1: Why the Doses Are Merely "Ballpark" Estimates With the rarest exceptions, actual surface doses are not measured during x-ray imaging procedures, even though small thermo-luminescent dosimeters (TLDs) have been shown not to interfere with images. Instead, some efforts have been made to measure doses on phantoms (dummies), but the limited exposure-circumstances during such tests provide unreliable dose information about exposures in real-world practice. After all, the very same equipment will deliver very different doses depending upon what settings and techniques the operator chooses (the first note in Table 1). Part 3: A Major New Addition to Evidence that X-Rays Are a Known Human Carcinogen In November 1999, a major prospective dose-response study of unique design provided what is probably the most powerful confirmation anywhere, that virtually all types of human cancer are inducible by medical x-rays in both males and females. The study is entitled Radiation from Medical Procedures in the Pathogenesis of Cancer and Ischemic Heart Disease: Dose-Response Studies with Physicians per 100,000 Population, and I am its author (Gofman 1999). That study has been independently peer-reviewed by a former chair of the BEIR Committee and former director of the National Cancer Institute (Arthur Upton, M.D.) and by a professor of physiology at Temple University School of Medicine (Prof. Howard S. Pitkow). Their comments are attached to this submission, after the Reference List. Although prospective dose-response studies are the "gold standard" in epidemiology for establishing causation, they are inherently unable to prove that some "mystery agent" is not the real cause of a positive dose-response. However, many lines of evidence in Gofman 1999 do virtually rule out explanations other than medical radiation as the cause of its incontrovertible positive correlations (discussion in Chapters 68 and 69). All-Cancers-Combined and Major Types, Males and Females Separately Gofman 1999 reveals that by 1940, medical radiation in the United States had become a necessary co-actor in about 90% of the age-adjusted male cancer mortality rate, and about 58% of the age-adjusted female cancer mortality rate (Chapter 6 and 7). These percentages cannot be dismissed as irrelevant today, because average annual per capita exposure to medical x-rays may not be substantially lower now than it was in the years preceding 1940 (discussion in Part 2, above). The prospective nature of the study is reflected by the fact that the 1940 age-adjusted national cancer mortality rates, for men and women separately, can be well predicted by analysis of the x-ray doses given in 1921 and 1931 (Gofman 1999, pp.213-214, p.222). Three Meritorious Scientific Differences from Other Studies The design of the 1999 study differs in three very positive ways from most other epidemiological analyses of low LET radiation. First, such analyses are often based a) on highly unreliable dose-estimates (because individual doses are not measured --- they are estimated later, often decades later) and (b) on highly unreliable estimates of risk per dose-unit (because such values derive from unreliable dose-estimates and/or from unreliable assumptions about the relative carcinogenic potency of particular types of low LET radiation). By contrast, the 1999 study avoids both of these pitfalls by using a sensible measure of relative accumulated x-ray exposure (Gofman 1999, Chapter 3). Second, other radiation studies sometimes use databases where the opportunity has existed for subjective choices, particularly on dosimetry and on exclusions. This is particularly true of the A-Bomb Survivor Database, whose practices --- of changing input after the results are known --- are discussed in both Gofman 1990 (Chapters 4, 5, 6) and Gofman 1999 (pp.43-44, pp.54-55). Moreover, influential analysts of that database have sometimes chosen to discard selected pieces of it. For example, the BEIR-1990 analysis discarded the observations from the 1950-1955 period except for breast cancer (BEIR p.168), discarded the observations from the two highest dose-groups (BEIR p.165), discarded cancer deaths which occurred beyond age 75 (BEIR p.165), and made no use of its own finding that the dose-response was supra-linear (BEIR p.200). By contrast, Gofman 1999 marries two databases which are utterly neutral with respect to radiation: The American Medical Association's database on physicians per 100,000 population, by the nation's nine Census Divisions, and the U.S. Vital Statistics on age-adjusted cancer mortality rates, by the nine Census Divisions. Moreover, the analysis does not discard data. Third, other radiation studies suffer from the problem of small numbers. Even the Life Span Study of the A-Bomb Survivors has a (repeatedly revised) database of only about 100,000 participants. Subdivision of cancer by types in such a study often produces statistically marginal findings. By contrast, the 1999 study of x-ray-induced cancer "enrolls" 130 million participants --- the entire 1940 population of the United States. For age-adjusted mortality rates for all cancers combined, by Census Divisions, the male dose-response with accumulated x-ray exposure has an R-squared value of 0.95, and for females, the value is 0.86. Subdivision of the data by the major types of cancer, separately for males and females, still yields highly significant dose-response relationships (summary table in Gofman 1999, p.217). The R-squared values are as follows: 0.92, 0.91, 0.76, 0.92, 0.94, 0.78, 0.72, 0.87, 0.96. The only exception to a highly significant, positive dose-response in all these studies was found in female genital cancers, with an R-squared value of 0.07. The Bottom Line: A Known Cause of Cancer, Lacking a Dose-Threshold We submit these data (Gofman 1999) as a major new addition to the human epidemiological evidence that x-rays are a known cause of human cancer. Part 4: The Absence of Any Risk-Free (Safe) Dose-Level of Low LET Radiation Gofman 1999 also presents (in its Appendix B) a nine-page summary of the overwhelming evidence that cancer risk from x-rays and gamma rays extends all the way down to zero dose (with excerpts from Gofman 1990, UNSCEAR 1993, and NRPB 1995). After publication of Gofman 1999, the finding of excess breast cancer in a study of scoliosis patients (Doody 2000) provided additional epidemiological evidence against any threshold dose. In the Doody study, the patients received x-radiation in serial doses which were estimated (long afterwards) at only 0.6 cGy (rad) per exam --- a dose which is the lowest conceivable dose (1 primary ionization track, on the average, per cell nucleus) with respect to DNA or chromosomal damage (Gofman 1999, p.522). By any reasonable standard of biomedical proof, the evidence from human epidemiology and the physical evidence from track-analysis combine to demonstrate that cellular repair processes, for nuclear DNA and chromosome injuries, are unable to deliver a safe (risk-free) dose of low-LET radiation --- including x-rays and gamma-rays. Part 5: Complex Mutations and Genomic Instability in Irradiated Cells There is a vast literature on human cell-studies which demonstrates that x-rays and gamma rays are a potent cause of structural chromosomal mutations of every sort, including re-arrangements, acentric fragments, and deletions ranging in size from multiple genes probably down to single nucleotides. (The deletion of a single nucleotide is no small matter, since it can scramble the genetic code by causing a frame-shift.) The dose-response shape for the easily detectable aberrations appears to be linear down to the 2 cGy dose-level (Lloyd 1992). One of the best sources, for evidence about the complex types of damage inflicted by low-LET radiation upon the human genome, are the studies by Ward (1991, 1994, 1995) and Sutherland (2000). Sutherland's observations include double-strand chromosome breaks (which are the basis for deletions, translocations and every other type of chromosomal re-arrangement) and other sorts of "clustered" DNA damage incorporating "two or more closely spaced damages" such as strand breaks, abasic sites and/or oxidized bases. Sutherland and colleagues are working experimentally with both gamma rays from cesium-137 and with 50 kVp x-rays (Sutherland 2000, p.107). In the same paper, Sutherland and colleagues conclude that their work confirms that each cluster "results from a single radiation track" (Sutherland 2000, p.106). If so, this constitutes additional support for the conclusion that there is no risk-free dose-level of exposure to x-rays and gamma-rays. The induction of single-strand and double-strand chromosome breaks by ionizing radiation is under study by Boudaiffa et al, who report on the role of the low-energy secondary electrons in strand breakage (Boudaiffa 2000). Induction of Genomic Instability by X-Rays and Gamma Rays Genomic instability refers to abnormally high rates (possibly accelerating rates) of genetic change occurring serially and spontaneously in cell-populations, as they descend from the same ancestral cell (Gofman 1999, p.533). Many (not all) cancer biologists now believe that genomic instability "is one of the most important aspects of carcinogenesis" (Morgan 1996, p.247; additional references and discussion in Gofman 1999, Appendix D). In 1976, Peter C. Nowell published his classic paper proposing that "the biological events recognized in tumor progression represent (i) the effects of acquired genetic instability in the neoplastic cells, and (ii) the sequential selection of variant subpopulations produced as a result of that genetic instability" (Nowell 1976, p.25). In 1971, I saw in our lab the operation of selective advantage for certain gamma-ray-induced mutations in cultured human fibroblasts: "There is no question that the cells with profound structural re-arrangements of chromosomes became the dominant and finally, with adequate survival time, the only reproducing cells in the culture" (Minkler 1971, p.73). Can exposure to x-rays and gamma-rays induce genomic instability? Evidence appears to support an affirmative answer. The following references (which provide many additional references) can be recommended: Holmberg 1993. Kronenberg 1994. Marder 1993. Mendonca 1993. Morgan 1996. # # # # # Reference List * BEIR 1990. Committee on the Biological Effects of Radiation, National Research Council, Health Effects of Exposure to Low Levels of Ionizing Radiation (BEIR-5 Report). 421 pages. ISBN 0-309-03995-9. National Academy Press, Washington DC. * Boudaiffa 2000. Badia Boudaiffa et al, "Resonant Formation of DNA Strand Breaks by Low-Energy (3 to 20 eV) Electrons," Science 287: 1658-1660. March 3, 2000. * Doody 2000. Michele M. Doody et al, "Breast Cancer Mortality after Diagnostic Radiography: Findings from the U.S. Scoliosis Cohort Study," Spine 25, No.16: 2052-2063. * FDA 1994. Food and Drug Administration, Public Health Advisory, "Avoidance of Serious X-Ray-Induced Skin Injuries to Patients during Fluoroscopically-Guided Procedures," Sept. 9, 1994. Six pages. US FDA, Ctr. for Devices and Radiological Health, Rockville MD 20857. * Gofman 1990. John W. Gofman, Radiation-Induced Cancer from Low-Dose Exposure: An Independent Analysis. 480 pages. ISBN 0-932682-89-8. CNR Books, San Francisco CA 94142. * Gofman 1996. John W. Gofman, Preventing Breast Cancer: The Story of a Major, Proven, Preventable Cause of This Disease. 422 pages. ISBN 0-932682-96-0. CNR Books, San Francisco CA 94142. * Gofman 1999. John W. Gofman, Radiation from Medical Procedures in the Pathogenesis of Cancer and Ischemic Heart Disease: Dose-Response Studies with Physicians per 100,000 Population. 699 pages. ISBN 0-932682-97-9. CNR Books, San Francisco CA 94142. * Gray 1998 a+b. Joel E. Gray, (a) "Lower Radiation Exposure Improves Patient Safety," Diagnostic Imaging Vol.20, No.9: 61-64. Sept. 1998. And (b) "Optimize X-Ray Systems to Minimize Radiation Dose," Vol.20, No.10: 62-70. Oct. 1998. * Holmberg 1993. Kerstin Holmberg et al, "Clonal Chromosome Aberrations and Genomic Instability in X-Irradiated Human T-Lymphocyte Cultures," Mutation Research 286: 321-330. * Huda 2000. Walter Huda et al, "Effective Doses to Patients Undergoing Thoracic Computed Tomography Examinations," Medical Physics Vol.27, No.5: 838-844. May 2000. * Koenig 2001 a+b. Titus R. Koenig et al, (a) "Skin Injuries from Fluoroscopically Guided Procedures: Part 1, Characteristics of Radiation Injury," American Journal of Roentgenology (AJR) 177: 3-11. And (b) "Part 2, Review of 73 Cases and Recommendations for Minimizing Dose Delivered to Patient," same issue, pp.13-20. July 2001. www.ajronline.org. * Kronenberg 1994. A. Kronenberg, "Radiation-Induced Genomic Instability," International Journal of Radiation Biology 66: 603-609. * Marder 1993. Brad A. Marder + William F. Morgan, "Delayed Chromosomal Instability Induced by DNA Damage," Molecular and Cell Biology 13: 6667-6677. * McCullough 2000. Cynthia H. McCullough + Beth A. Schueler, "Calculation of Effective Dose: Educational Treatise," Medical Physics Vol.27, No.5: 828-837. May 2000. * Mendonca 1993. Marc S. Mendonca et al, "Delayed Heritable Damage and Epigenetics in Radiation-Induced Neoplastic Transformation of Human Hybrid Cells, Radiation Research 134: 209-216. * Mettler 2000. Fred A Mettler et al, "CT Scanning: Patterns of Use and Dose," Journal of Radiation Protection 20: 353-359. * Minkler 1971. Jason L. Minkler + D. Piluso + J.W. Gofman + R.K. Tandy, "A Long-Term Effect of Radiation on Chromosomes of Cultured Human Fibroblasts," Mutation Research 13: 67-75. * Morgan 1996. William F. Morgan et al, "Genomic Instability Induced by Ionizing Radiation" (review), Radiation Research 146: 247-258. * NCRP 1989. National Council on Radiation Protection and Measurements, Exposure of the U.S. Population from Diagnostic Medical Radiation. Report 100. 105 pages. www.ncrp.com * Nickoloff 2001. Edward L. Nickoloff + Philip O. Alderson, "Radiation Exposures to Patients from CT: Reality, Public Perception, and Policy," (Commentary), American J. of Roentgenology (AJR) 177: 285-287. August 2001. www.ajronline.org. * Nowell 1976. Peter C. Nowell, " Clonal Evolution of Tumor Cell Populations," Science 194: 23-28. * NRPB 1995. National Radiological Protection Board (Britain), Risk of Radiation-Induced Cancer at Low Doses and Low Dose Rates for Radiation Protection Purposes. 77 pages. ISBN 0-85951-386-6. * Ravenel 2001. James G. Ravenel et al, "Radiation Exposure and Image Quality in Chest CT Examinations," American Journal of Roentgenology (AJR) 177: 279-284. August 2001. * Shope 1996. Thomas B. Shope, "Radiation-Induced Skin Injuries from Fluoroscopy," Radiographics Vol.16, No.5: 1195-1199. * Shope 1997. Thomas B. Shope, "Proposed Fluoroscopic Amendments," memo and letter March 18, 1997 to "Fluoroscopic X-Ray System Manufacturers, Users, and Other Interested Parties." FDA Ctr. for Devices and Radiological Health, Rockville MD 20857. * Sutherland 2000. Betsy M. Sutherland et al, "Clustered DNA Damages Induced in Isolated DNA and in Human Cells by Low Doses of Ionizing Radiation," Proceedings of the National Academy of Sciences Vol.97, No.1: 103-108. January 4, 2000. www.pnas.org/cgi/content/full/97/1/103. * UNSCEAR 1993. United Nations Scientific Committee on the Effects of Atomic Radiation, Sources and Effects of Ionizing Radiation, with Scientific Annexes. 922 pages. ISBN 92-1-142200-0. * Ware 1999. Dan E. Ware et al, "Radiation Effective Doses to Patients Undergoing Abdominal CT Examinations," Radiology Vol.210, No.3: 645-650. March 1999. Peer-Review The following links include the peer-reviewed contents included with this report: * CHOICE Current Reviews for Academic Libraries The above link goes to the ChoiceReviews.online site which is subscriber-only. ChoiceReviews.online does offer a free two-month trial subscription service. Dr. Gofman's 1999 monograph, Radiation from Medical Procedures in the Pathogenesis of Cancer and Ischemic Heart Disease: Dose-Response Studies with Physicians per 100,000 Population is favorably reviewed in the May 2000 issue of CHOICE, Health Sciences Section, number 37-5129, Library of Congress CIP number 99-45096. The reviewer is Howard S. Pitkow, Ph.D., Professor Emeritus of Physiology, Temple University School of Medicine, Philadelphia. * Some Comments about Dr. John Gofman's Earlier Work and Books * News Release, Univ. of California, Berkeley, Nov. 16, 1999: Radiation Expert Warns of Danger from Overuse of Medical X-rays, Claiming They Are Responsible for Many Cancer and Heart Disease Deaths --------------------------------------------------- | | | XaHP: The X-rays and Health Project. | | An educational project of the | | Committee for Nuclear Responsibility. | |_________________________________________________| --------------------------------------------------------- | The plan: Lower x-ray doses per x-ray procedure. | | The result: Fewer cases of x-ray-induced cancer | | and coronary heart disease. | |_______________________________________________________| This document is available electronically at: http://www.ratical.org/radiation/CNR/NTP.html (hyper text) http://www.ratical.org/radiation/CNR/NTP.txt (ascii text)