Complexity of chromosomal aberrations and gene expression changes in human blood lymphocytes after exposure to alpha particle radiation

Abstract

Background: Targeted alpha therapy (TAT) is emerging as an effective treatment modality of cancer especially for micrometastasis, lymphoproliferative malignancies, and palliative approaches of bone cancer. Human blood lymphocytes may encounter alpha (a) exposure while traversal of targeted a particle emitting radio isotopes to the tumor site, due to their nonspecificity and release of radio isotopes from the legends used for targeting. Such radiation effects to lymphocytes may be implicated in short and long term health effects during TAT. Aims and Objectives: To see the effects of a-particle in blood lymphocytes and to compare their complexity of aberration with both and X-rays. Materials and Methods: Chromosomal aberrations such as dicentric chromosome, micronuclei, nucleoplasmic bridge (NPB) in the peripheral blood lymphocytes were scored for both a alpha particle and X rays. Then, the chromosome aberrations (CA) frequency was correlated with the gene expression (FDXR, CDKN1A and GADD45A) to both the type of radiations. Results: CA induced by a radiation was complex and highly dispersed when compared to low LET radiation. Moreover, magnitude of NPB was significantly higher in case of a radiation than radiation. A dose dependent increase in gene expression (FDXR, CDKN1A and GADD45) was observed after a radiation, which however, was higher in case of a radiation than X rays. Conclusion: These results provide better understanding about effects of a radiation on human lymphocytes, which may be significant implications in developing better TAT strategies for cancer.

Keywords

• alpha particles
• chromosomal aberration
• gene expression