Bruenger F W, Lloyd R D, Miller S C, Taylor G N, Angus W, Huth D A
Radiobiology Division, School of Medicine, University of Utah, Salt Lake City 84112.
Radiat Res. 1994 Jun;138(3):423-34.
A total of 128 primary mammary tumors (66 of them malignant) occurred in 35 female beagles injected with 226Ra 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 226Ra 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-->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. Results of this study are potentially useful in understanding risks of radium-induced breast cancers in humans.
共有128个原发性乳腺肿瘤（其中66个为恶性）出现在35只成年雌性比格犬身上，这些犬在年轻时被注射了226Ra，剂量水平从0.2至440 kBq/kg体重，共8个剂量等级。而在46只未接受任何放射性物质的雌性对照比格犬中，共发现了156个乳腺肿瘤（其中57个为恶性）。65只对照犬中的63只以及接受226Ra的61只犬中的59只存活至诊断乳腺肿瘤的最小年龄3.75岁。根据对照组中观察到的年龄依赖性肿瘤发生率以及相应的犬年风险数量，镭组中观察到的恶性肿瘤总数在统计学上显著高于预期恶性肿瘤数量（观察到66个，预期34个，P < 0.005）。良性肿瘤则没有这种差异。Cox回归分析表明，受辐照犬首次发生肿瘤的风险没有增加。对多变量风险集的Cox回归分析显示，良性肿瘤发生的风险没有显著增加，但恶性肿瘤发生的风险在统计学上更高，为1.66，置信区间为1.15 - 2.40。风险增加取决于剂量，但无法证实与先前乳腺肿瘤发生频率有关。在手术时对卵巢切除的犬进行截尾处理，相对风险略有降低，但不改变显著性。累积暴露低于0.2 Gy的诊断性X射线照射对肿瘤形成没有影响。尚不清楚恶性乳腺肿瘤风险增加是由于镭在敏感组织中的一些初始沉积、短暂的氡→钋沉积对脂肪乳腺组织的可能照射，还是镭的总体沉积对犬免疫系统的一般影响，从而降低了它们对乳腺肿瘤形成的抵抗力。本研究结果可能有助于理解镭诱发人类乳腺癌的风险。
