University of Nevada Las Vegas, Las Vegas, Nevada.
Lawrence Berkeley National Laboratory, Biological Systems and Engineering Division, Berkeley, California.
Int J Radiat Oncol Biol Phys. 2021 Apr 1;109(5):1521-1532. doi: 10.1016/j.ijrobp.2020.11.039. Epub 2020 Nov 21.
Computed tomographic (CT) scans in adolescents have increased dramatically in recent years. However, the effects of cumulative low-dose exposures on the development of radiation sensitive organs, such as the mammary gland, is unknown. The purpose of this work was to define the effects of dose rate on mammary organ formation during puberty, an especially sensitive window in mammary development. We used a fractionated low-dose x-ray exposure to mimic multiple higher dose CT scans, and we hypothesized that fractionated exposure would have less of an effect on the number of mammary gland defects compared with an acute exposure.
Female mice were subjected to fractionated low-dose x-ray exposure (10 cGy/d for 5 days), acute x-ray exposure (1 × 50 cGy), or sham exposure. As the wide genetic diversity in humans can play a role in a person's response to irradiation, 2 genetically diverse mouse strains differing in radiation sensitivity (BALB/c-sensitive; C57BL/6-resistant) were used to investigate the role of genetic background on the magnitude of the effect.
Unexpectedly, our data reveal that multiple low-dose exposures produce greater immune and mammary defects for weeks after exposure compared with controls. The most pronounced defects being increased ductal branching in both strains and a greater percentage of terminal end buds in the BALB/c strain of mice exposed to fractionated radiation compared with sham. Radiation-induced defects near the terminal end bud were also increased in both strains.
The findings suggest that fractionated low-dose exposures are potentially more damaging to organ development compared with an equivalent, single acute exposure and that genetic background is an important parameter modifying the severity of these effects.
近年来，青少年的计算机断层扫描（CT）检查数量急剧增加。然而，累积低剂量暴露对辐射敏感器官（如乳腺）发育的影响尚不清楚。本研究的目的是确定剂量率对青春期乳腺器官形成的影响，因为青春期是乳腺发育的一个特别敏感的时期。我们使用分次低剂量 X 射线照射来模拟多次更高剂量 CT 扫描，并且假设分次照射对乳腺缺陷数量的影响将小于急性照射。
雌性小鼠接受分次低剂量 X 射线照射（10 cGy/d，共 5 天）、单次急性 X 射线照射（1×50 cGy）或假照射。由于人类广泛的遗传多样性可能在一个人对辐射的反应中发挥作用，因此使用 2 种遗传多样性不同的对辐射敏感程度不同的小鼠品系（BALB/c 敏感；C57BL/6 抗性）来研究遗传背景对效应大小的作用。
出乎意料的是，我们的数据显示，与对照组相比，多次低剂量暴露在暴露后数周内会产生更大的免疫和乳腺缺陷。最明显的缺陷是两种品系的导管分支增加，以及暴露于分次辐射的 BALB/c 品系小鼠的终末芽数量增加。两种品系中靠近终末芽的辐射诱导缺陷也增加了。
这些发现表明，与等效的单次急性暴露相比，分次低剂量暴露对器官发育具有潜在的更大破坏性，并且遗传背景是修饰这些效应严重程度的重要参数。
