Department of Environmental and Occupational Health, Fay W. Boozman College of Public Health, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
Department of Biochemistry and Molecular Biology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
Int J Radiat Biol. 2023;99(4):644-655. doi: 10.1080/09553002.2022.2110319. Epub 2022 Aug 15.
Nuclear weapons testing in the northern Marshall Islands between 1946 and 1958 resulted in ionizing radiation (IR) exposure of the thousands of Marshallese. Furthermore, numerous islands were contaminated by radioactive fallout. Significant increases in cancer and metabolic syndrome incidences have been reported among Marshallese, and potential for further increases looms due to the latency of radiation-induced health effects. The purpose of this study was to investigate the genetic and epigenetic effects of exposure to IR that could be associated with radiation-induced disease among the Northwest Arkansas (NWA) Marshallese.
We performed analysis of chromosomal aberrations and DNA methylation based on residential and exposure history of NWA Marshallese.
Analysis of chromosomal aberrations demonstrated higher incidence of genetic rearrangements in women with self-reported history of radiation exposure (95% CI: 0.10, 1.22; =.022). Further clustering of study participants based on their residential history demonstrated that participants who spent substantial amounts of time (≥6 months) in the northern atolls (thus, in the proximity of nuclear tests) before 1980 had more chromosomal aberrations than their peers who lived only in the southern atolls (95% CI: 0.08, -0.95; =.021), and that this difference was driven by women. A relationship between the time spent in the northern atolls and increase in chromosomal aberrations was observed: 0.31 increase in chromosomal aberrations for every 10 years spent at northern atolls (95% CI: 0.06, 0.57; =.020). Finally, significant inverse correlations between the chromosomal aberrations and the extent of DNA methylation of four LINE-1 elements L1PA2, L1PA16, L1PREC1, and L1P4B were identified.
The results of this study provide first evidence of the presence of stable genetic and epigenetic rearrangements in peripheral lymphocytes of NWA Marshallese and warrant further studies to analyze the role of radiation exposure in health disparities experienced by this Pacific Island nation.
1946 年至 1958 年间，在马绍尔群岛北部进行的核武器试验导致数千名马绍尔人受到电离辐射（IR）照射。此外，许多岛屿受到放射性沉降物的污染。据报道，马绍尔群岛的癌症和代谢综合征发病率显著增加，由于辐射诱发的健康影响潜伏期，未来发病率可能进一步增加。本研究的目的是调查与马绍尔群岛西北（NWA）居民接触 IR 相关的遗传和表观遗传效应，这些效应可能与辐射引起的疾病有关。
我们根据 NWA 马绍尔人的居住和暴露史，对染色体畸变和 DNA 甲基化进行了分析。
染色体畸变分析表明，有自我报告辐射暴露史的女性遗传重排发生率更高（95%CI：0.10，1.22；=.022）。进一步根据研究参与者的居住史进行聚类分析表明，1980 年前在北部环礁（因此，靠近核试验地点）居住时间较长（≥6 个月）的参与者的染色体畸变比仅在南部环礁居住的同龄人多（95%CI：0.08，-0.95；=.021），这种差异是由女性驱动的。观察到在北部环礁居住的时间与染色体畸变增加之间存在关系：在北部环礁居住的每增加 10 年，染色体畸变增加 0.31（95%CI：0.06，0.57；=.020）。最后，发现染色体畸变与四个 LINE-1 元件 L1PA2、L1PA16、L1PREC1 和 L1P4B 的 DNA 甲基化程度之间存在显著的负相关关系。
本研究结果首次提供了 NWA 马绍尔人外周淋巴细胞存在稳定遗传和表观遗传重排的证据，并需要进一步研究来分析辐射暴露在这个太平洋岛国健康差异中的作用。
