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Title: Occurrence of mammary tumors in beagls given radium-226

Abstract

A total of 128 primary mammary tumors (66 of them malignant) occurred in 35 female beagles injected with {sup 226}Ra at eight dose levels ranging from 0.2 to 440 kBq/kg body mass as young adults, while a total of 156 mammary tumors (57 of them malignant) were seen in 46 female control beagles not given any radioactivity. Sixty-three of 65 control dogs and 59 of 61 dogs given {sup 226}Ra survived the minimum age for diagnosis of mammary tumors of 3.75 years. Based on the observed age-dependent tumor incidence rates in the controls and on the corresponding number of dog-years at risk, the total number of observed malignant tumors in the radium group was statistically greater than the number of expected malignant tumors (66 observed vs 34 expected, P < 0.005). There was no such difference for the benign tumors. Cox regression analysis indicated no increased risk for the first tumor occurrence in irradiated dogs. Cox regression analysis of the multivariate risk sets showed no significantly increased risk for the occurrence of benign tumors but a statistically higher risk of 1.66 with a confidence interval of 1.15-2.40 for the occurrence of malignant tumors. The increased risk was dependent on dose,more » but a dependence on the frequency of previous occurrence of mammary tumors could not be confirmed. Censoring ovariectomized dogs at time of surgery decreased the relative risks slightly but did not alter the significance. Exposure to diagnostic X rays with cumulative exposures below 0.2 Gy had no effect on tumor formation. It is unknown whether the increased risk for malignant mammary tumors was due to some initial deposition of radium in sensitive tissue, a possible irradiation of fatty mammary tissue from transient radon {yields} polonium deposition, or a general effect of the overall radium deposition on the immune system of the dogs that lowered their resistance to formation of mammary tumors. 27 refs., 5 figs., 4 tabs.« less

Authors:
; ; ; ; ;  [1]
  1. Univ. of Utah, Salt Lake City, UT (United States)
Publication Date:
Sponsoring Org.:
USDOE
OSTI Identifier:
79321
DOE Contract Number:
AC02-76EV00119; AC04-76EV01013
Resource Type:
Journal Article
Resource Relation:
Journal Name: Radiation Research; Journal Volume: 138; Journal Issue: 3; Other Information: PBD: Jun 1994
Country of Publication:
United States
Language:
English
Subject:
56 BIOLOGY AND MEDICINE, APPLIED STUDIES; RADIUM 226; DOSE-RESPONSE RELATIONSHIPS; MAMMARY GLANDS; NEOPLASMS; DISEASE INCIDENCE; RADIOINDUCTION; BEAGLES; REGRESSION ANALYSIS; YIELDS

Citation Formats

Bruenger, F.W., Lloyd, R.D., Miller, S.C., Taylor, G.N., Angus, W., and Huth, D.A. Occurrence of mammary tumors in beagls given radium-226. United States: N. p., 1994. Web. doi:10.2307/3578692.
Bruenger, F.W., Lloyd, R.D., Miller, S.C., Taylor, G.N., Angus, W., & Huth, D.A. Occurrence of mammary tumors in beagls given radium-226. United States. doi:10.2307/3578692.
Bruenger, F.W., Lloyd, R.D., Miller, S.C., Taylor, G.N., Angus, W., and Huth, D.A. 1994. "Occurrence of mammary tumors in beagls given radium-226". United States. doi:10.2307/3578692.
@article{osti_79321,
title = {Occurrence of mammary tumors in beagls given radium-226},
author = {Bruenger, F.W. and Lloyd, R.D. and Miller, S.C. and Taylor, G.N. and Angus, W. and Huth, D.A.},
abstractNote = {A total of 128 primary mammary tumors (66 of them malignant) occurred in 35 female beagles injected with {sup 226}Ra at eight dose levels ranging from 0.2 to 440 kBq/kg body mass as young adults, while a total of 156 mammary tumors (57 of them malignant) were seen in 46 female control beagles not given any radioactivity. Sixty-three of 65 control dogs and 59 of 61 dogs given {sup 226}Ra survived the minimum age for diagnosis of mammary tumors of 3.75 years. Based on the observed age-dependent tumor incidence rates in the controls and on the corresponding number of dog-years at risk, the total number of observed malignant tumors in the radium group was statistically greater than the number of expected malignant tumors (66 observed vs 34 expected, P < 0.005). There was no such difference for the benign tumors. Cox regression analysis indicated no increased risk for the first tumor occurrence in irradiated dogs. Cox regression analysis of the multivariate risk sets showed no significantly increased risk for the occurrence of benign tumors but a statistically higher risk of 1.66 with a confidence interval of 1.15-2.40 for the occurrence of malignant tumors. The increased risk was dependent on dose, but a dependence on the frequency of previous occurrence of mammary tumors could not be confirmed. Censoring ovariectomized dogs at time of surgery decreased the relative risks slightly but did not alter the significance. Exposure to diagnostic X rays with cumulative exposures below 0.2 Gy had no effect on tumor formation. It is unknown whether the increased risk for malignant mammary tumors was due to some initial deposition of radium in sensitive tissue, a possible irradiation of fatty mammary tissue from transient radon {yields} polonium deposition, or a general effect of the overall radium deposition on the immune system of the dogs that lowered their resistance to formation of mammary tumors. 27 refs., 5 figs., 4 tabs.},
doi = {10.2307/3578692},
journal = {Radiation Research},
number = 3,
volume = 138,
place = {United States},
year = 1994,
month = 6
}
  • Comparison of 120 young adult female beagles given 0.026 to 106 kBq {sup 239}Pu kg{sup -1} by intravenous injection and 63 comparable female control beagles showed that there were no significant differences in the risk of mammary tumor appearance between the two groups. This was the case for benign tumors only, for malignant tumors only, and for both malignant and benign tumors considered together. for malignant tumors the observed number was 73 as compared with 69 expected; for benign tumors, there were 131 observed and 126 expected; for all tumors (separate analysis, not just the addition of malignant plus benign),more » there were 199 observed and 199 expected. Chi-square analysis indicated that the p values for all these comparisons were >0.05. There were 45 controls (71.4%) with any tumor vs. 67 dogs (55.8%) given Pu (95% C.I. = 46.9% to 86.2%). No significant differences could be established (Kaplan-Meier analysis) between these two groups for survival age at diagnosis of the first mammary tumor, 11.75 {+-} 0.30 y for dogs given Pu vs. 11.90 {+-} 0.36 y for controls. We reported previously that differences in mammary cancer occurrence had been identified between this same group of control dogs and 57 female beagles given {sup 226}Ra as young adults. The present study appears to support the earlier conclusion that something other than alpha irradiation of the skeleton (both {sup 226}Ra and {sup 239}Pu deposit in bone) seems to affect the appearance of mammary cancers, since internally deposited {sup 226}Ra does appear to induce these malignancies, possibly from initial deposition in mammary tissue of the parent radionuclide or the subsequent concentration in sensitive tissue of its radioactive progeny, {sup 222}Rn or isotopes of polonium, lead, and bismuth, which are absent in the case of {sup 239}Pu. 15 refs., 5 tabs.« less
  • The RBE for tritium was estimated in reference to 200-kVp X rays, using acceleration of breast tumor appearance in the female Sprague-Dawley rat as the end-point. Seventy-five percent of the total tritium dose was delivered to the mammary gland within the first 10 days and 95% within the first 20 days after the start of the tritium exposure. RBE estimations were based on various criteria including the tumor incidence per Gy at 450 days postirradiation and the time required to induce tumors in 50% of the animals at risk. The results suggest that tritium ..beta.. rays are about 1.1-1.3 timesmore » more effective than chronic 200-kVp X rays for acceleration of the appearance of rat mammary tumors. However, the uncertainties involved in these calculations are such that the effects of tritium ..beta.. rays could not be reliably distinguished from those of chronic 200-kVp X rays. Measured differences in RBE values were slightly larger for the comparison between acute and chronic X rays than for the comparison between chronic tritium ..beta.. rays and chronic X rays.« less
  • The Fab fragments of antibodies against cell-type-specific surface antigens of mouse mammary epithelial cells (MME-antigens) were used to localize mammary tumors successfully. The radioiodine-labeled anti-MME (Fab) was injected into mice carrying simulated mammary metastases, and after 24 hours the amount of label per gram of excised tissue was several times greater in the tumor than in liver, brain, lung, or muscle. Kidney showed considerable accumulation of label but this appeared to be nonspecific. Kinetic studies revealed a rapid elimination of labeled Fab in the urine with only 1% of the injected dose remaining in the entire blood pool after 24more » hours. Wit a high-purity germanium camera, mammary tumors were clearly located ty the /sup 131/I-labeled anti-MME (Fab), and normalization to /sup 99m/Tc-pertechnetate distribution in the animal increased the specificity. The density of /sup 131/I-label was fourfold greater over the mammary tumor than over comparable areas of the mouse. No accumulation of /sup 131/I-anti-MME (Fab) was observed in nonmammary tumors nor in mammary tumors when labeled nonspecific Fab was used. An analogous system using an antihuman mammary epithelial antiserum is being developed for localization of breast metastases in humans.« less