{"title":"区域人群中的候选基因表达及其与辐射分流的相关性。","authors":"Nandhini Kannan, Teena Koshy, Venkateswarlu Raavi, Emmanuel Bhaskar, Swathy Moorthy, Venkata Sai Pulivadula Mohanarangam, Satish Srinivas Kondaveeti, Shangamithra Visweswaran, Venkatachalam Perumal","doi":"10.1159/000531258","DOIUrl":null,"url":null,"abstract":"<p><p>Quantification of gene expression signatures has been substantiated as a potential and rapid marker for radiation triage and biodosimetry during nuclear emergencies. Similar to the established biodosimetry assays, the gene expression assay has drawbacks such as being highly dynamic and transient, not specific to ionizing radiation, and also influenced by confounding factors such as gender, health status, lifestyle, and inflammation. In view of that, prior knowledge of baseline expression of certain candidate genes in a population could complement the discrimination of the unexposed from the exposed individuals without the need for individual pre-exposure controls. We intended to establish a baseline expression of reported radiation-responsive genes such as CDKN1A, DDB2, FDXR, and PCNA in the blood samples of healthy human participants and then compare it with diabetic/hypertension participants (as a chronic inflammatory condition) drawn from south Indian population. Further, we have examined the appropriateness of the assay for radiation triage-like situations; i.e., the expression profiles of those genes were examined in the participants who underwent X-ray-based medical imaging. Acute inflammation induced by lipopolysaccharide exposure in the blood significantly increased the fold expression of those genes (p < 0.0001) compared to the control. Whereas the basal expression level of those genes among the participants with the inflammatory condition is marginally higher than those observed in the healthy participants; despite the excess, the fold increase in those genes between the groups did not differ significantly. Consistent with the inflammatory participants, the basal expression level of those genes in the blood sample of participants who received X-radiation during neuro-interventional and computed tomography imaging is marginally higher than those observed in the pre-exposure of respective groups. Nevertheless, the fold increase in those genes did not differ significantly as the fold change fell within the two folds. Thus, overall results suggest that the utility of CDKN1A, DDB2, FDXR, and PCNA gene expression for radiation triage specific after very low-dose radiation exposure needs to be interpreted with caution for a much more reliable triage.</p>","PeriodicalId":11206,"journal":{"name":"Cytogenetic and Genome Research","volume":null,"pages":null},"PeriodicalIF":1.7000,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Candidate Gene Expression in Regional Population and Its Relevance for Radiation Triage.\",\"authors\":\"Nandhini Kannan, Teena Koshy, Venkateswarlu Raavi, Emmanuel Bhaskar, Swathy Moorthy, Venkata Sai Pulivadula Mohanarangam, Satish Srinivas Kondaveeti, Shangamithra Visweswaran, Venkatachalam Perumal\",\"doi\":\"10.1159/000531258\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Quantification of gene expression signatures has been substantiated as a potential and rapid marker for radiation triage and biodosimetry during nuclear emergencies. Similar to the established biodosimetry assays, the gene expression assay has drawbacks such as being highly dynamic and transient, not specific to ionizing radiation, and also influenced by confounding factors such as gender, health status, lifestyle, and inflammation. In view of that, prior knowledge of baseline expression of certain candidate genes in a population could complement the discrimination of the unexposed from the exposed individuals without the need for individual pre-exposure controls. We intended to establish a baseline expression of reported radiation-responsive genes such as CDKN1A, DDB2, FDXR, and PCNA in the blood samples of healthy human participants and then compare it with diabetic/hypertension participants (as a chronic inflammatory condition) drawn from south Indian population. Further, we have examined the appropriateness of the assay for radiation triage-like situations; i.e., the expression profiles of those genes were examined in the participants who underwent X-ray-based medical imaging. Acute inflammation induced by lipopolysaccharide exposure in the blood significantly increased the fold expression of those genes (p < 0.0001) compared to the control. Whereas the basal expression level of those genes among the participants with the inflammatory condition is marginally higher than those observed in the healthy participants; despite the excess, the fold increase in those genes between the groups did not differ significantly. Consistent with the inflammatory participants, the basal expression level of those genes in the blood sample of participants who received X-radiation during neuro-interventional and computed tomography imaging is marginally higher than those observed in the pre-exposure of respective groups. Nevertheless, the fold increase in those genes did not differ significantly as the fold change fell within the two folds. Thus, overall results suggest that the utility of CDKN1A, DDB2, FDXR, and PCNA gene expression for radiation triage specific after very low-dose radiation exposure needs to be interpreted with caution for a much more reliable triage.</p>\",\"PeriodicalId\":11206,\"journal\":{\"name\":\"Cytogenetic and Genome Research\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.7000,\"publicationDate\":\"2023-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cytogenetic and Genome Research\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1159/000531258\",\"RegionNum\":4,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2023/5/30 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q4\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cytogenetic and Genome Research","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1159/000531258","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/5/30 0:00:00","PubModel":"Epub","JCR":"Q4","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
基因表达特征的量化已被证实是核紧急情况下辐射分流和生物模拟的潜在快速标记。与已有的生物剂量测定方法类似,基因表达检测法也存在一些缺点,如动态性和瞬时性强,对电离辐射不具有特异性,还受性别、健康状况、生活方式和炎症等干扰因素的影响。有鉴于此,事先了解人群中某些候选基因的基线表达情况,可以辅助区分未受辐射和受辐射个体,而无需进行个体辐射前对照。我们打算在健康人的血液样本中确定 CDKN1A、DDB2、FDXR 和 PCNA 等已报道的辐射反应基因的基线表达,然后与来自南印度人群的糖尿病/高血压患者(作为一种慢性炎症)进行比较。此外,我们还研究了该检测方法在类似辐射分流情况下的适用性;即在接受 X 射线医学成像的参与者中检测这些基因的表达谱。与对照组相比,血液中脂多糖暴露诱发的急性炎症明显增加了这些基因的表达倍数(p < 0.0001)。尽管这些基因在炎症参与者中的基础表达水平略高于在健康参与者中观察到的水平,但这些基因在不同组间的表达倍增并无明显差异。与炎症参与者的情况一致,在神经介入和计算机断层扫描成像过程中接受 X 射线照射的参与者的血液样本中,这些基因的基础表达水平略高于各组暴露前的水平。尽管如此,这些基因的增加倍数并无显著差异,因为其变化倍数均在两个倍数之内。因此,总体结果表明,CDKN1A、DDB2、FDXR 和 PCNA 基因表达在极低剂量辐射照射后的辐射分流中的作用需要谨慎解释,以便进行更可靠的分流。
Candidate Gene Expression in Regional Population and Its Relevance for Radiation Triage.
Quantification of gene expression signatures has been substantiated as a potential and rapid marker for radiation triage and biodosimetry during nuclear emergencies. Similar to the established biodosimetry assays, the gene expression assay has drawbacks such as being highly dynamic and transient, not specific to ionizing radiation, and also influenced by confounding factors such as gender, health status, lifestyle, and inflammation. In view of that, prior knowledge of baseline expression of certain candidate genes in a population could complement the discrimination of the unexposed from the exposed individuals without the need for individual pre-exposure controls. We intended to establish a baseline expression of reported radiation-responsive genes such as CDKN1A, DDB2, FDXR, and PCNA in the blood samples of healthy human participants and then compare it with diabetic/hypertension participants (as a chronic inflammatory condition) drawn from south Indian population. Further, we have examined the appropriateness of the assay for radiation triage-like situations; i.e., the expression profiles of those genes were examined in the participants who underwent X-ray-based medical imaging. Acute inflammation induced by lipopolysaccharide exposure in the blood significantly increased the fold expression of those genes (p < 0.0001) compared to the control. Whereas the basal expression level of those genes among the participants with the inflammatory condition is marginally higher than those observed in the healthy participants; despite the excess, the fold increase in those genes between the groups did not differ significantly. Consistent with the inflammatory participants, the basal expression level of those genes in the blood sample of participants who received X-radiation during neuro-interventional and computed tomography imaging is marginally higher than those observed in the pre-exposure of respective groups. Nevertheless, the fold increase in those genes did not differ significantly as the fold change fell within the two folds. Thus, overall results suggest that the utility of CDKN1A, DDB2, FDXR, and PCNA gene expression for radiation triage specific after very low-dose radiation exposure needs to be interpreted with caution for a much more reliable triage.
期刊介绍:
During the last decades, ''Cytogenetic and Genome Research'' has been the leading forum for original reports and reviews in human and animal cytogenetics, including molecular, clinical and comparative cytogenetics. In recent years, most of its papers have centered on genome research, including gene cloning and sequencing, gene mapping, gene regulation and expression, cancer genetics, comparative genetics, gene linkage and related areas. The journal also publishes key papers on chromosome aberrations in somatic, meiotic and malignant cells. Its scope has expanded to include studies on invertebrate and plant cytogenetics and genomics. Also featured are the vast majority of the reports of the International Workshops on Human Chromosome Mapping, the reports of international human and animal chromosome nomenclature committees, and proceedings of the American and European cytogenetic conferences and other events. In addition to regular issues, the journal has been publishing since 2002 a series of topical issues on a broad variety of themes from cytogenetic and genome research.