Radiation Protection Research and Instrumentation Branch, Atomic Energy of Canada Limited, Chalk River Laboratories, Chalk River, Ontario K0J 1J0, Canada.
Radiat Res. 2010 Jan;173(1):40-8. doi: 10.1667/RR1875.1.
This report tests the hypotheses that cancer proneness elevates risk from a high radiation exposure and that the risk response to high doses is qualitatively similar to that from low doses. Groups of about 170 female mice heterozygous for Trp53 (Trp53(+/-)) and their normal female littermates (Trp53(+/+)) were exposed at 7-8 weeks of age to (60)Co gamma-radiation doses of 0, 1, 2, 3 or 4 Gy at a high dose rate (0.5 Gy/min) or 4 Gy at a low dose rate (0.5 mGy/min). In the absence of radiation exposure, Trp53 heterozygosity reduced life span approximately equally for death from either cancer or non-cancer disease. Heterozygosity alone produced a 1.5-fold greater shortening of life span than a 4-Gy acute exposure. Per unit dose, life shortening from cancer or non-cancer disease was the same for normal mice and Trp53 heterozygous animals, indicating that, contrary to previous reports, Trp53 heterozygosity did not confer radiation sensitivity to high doses of gamma rays. In Trp53(+/-) mice with cancer, life shortening from acute doses up to 4 Gy was related to both increased tumor formation and decreased tumor latency. A similar tumor response was observed in normal mice, but only up to 2 Gy, indicating that above 2 Gy, normal Trp53 function protected against tumor initiation, and further life shortening reflected only decreased latency for cancer and non-cancer disease. Dose-rate reduction factors were 1.7-3.0 for both genotypes and all end points. We conclude that Trp53 gene function influences both cancer and non-cancer mortality in unexposed female mice and that Trp53-associated cancer proneness in vivo is not correlated with elevated radiation risk. Increased risk from high acute radiation doses contrasts with the decreased risk seen previously after low doses of radiation in both Trp53 normal and heterozygous female mice.
一是易患癌症会增加高辐射暴露的风险；二是高剂量和低剂量的风险反应本质上是相似的。大约 170 只 7-8 周龄的杂合 Trp53（Trp53(+/-)）雌性小鼠及其正常的同窝雌性小鼠（Trp53(+/+)）被暴露于（60）Co γ射线中，辐射剂量分别为 0、1、2、3 或 4 Gy，剂量率较高（0.5 Gy/min）或 4 Gy，剂量率较低（0.5 mGy/min）。在没有辐射暴露的情况下，Trp53 杂合性使因癌症或非癌症疾病导致的寿命缩短约相等。杂合性本身导致的寿命缩短比 4 Gy 急性暴露长 1.5 倍。对于正常小鼠和 Trp53 杂合动物，每单位剂量的癌症或非癌症疾病导致的寿命缩短是相同的，这表明与先前的报告相反，Trp53 杂合性不会增加对高剂量 γ射线的辐射敏感性。在有癌症的 Trp53(+/-)小鼠中，从急性剂量高达 4 Gy 的寿命缩短与肿瘤形成增加和肿瘤潜伏期缩短有关。在正常小鼠中也观察到类似的肿瘤反应，但仅限于 2 Gy 以下，这表明在 2 Gy 以上，正常的 Trp53 功能可防止肿瘤发生，进一步的寿命缩短仅反映了癌症和非癌症疾病的潜伏期缩短。对于两种基因型和所有终点，剂量率降低因子为 1.7-3.0。我们得出结论，Trp53 基因功能会影响未暴露的雌性小鼠的癌症和非癌症死亡率，并且体内 Trp53 相关的癌症易感性与增加的辐射风险无关。高急性辐射剂量的风险增加与先前在 Trp53 正常和杂合雌性小鼠中观察到的低剂量辐射后风险降低形成对比。
