Validating Baboon Ex Vivo and In Vivo Radiation-Related Gene Expression with Corresponding Human Data

Area of Science:

• Biomedical Sciences
• Radiation Biology
• Genomics

Background:

• High-throughput diagnostic tests are crucial for managing radio/nuclear incidents.
• Previous research identified candidate genes in baboons for predicting hematologic acute radiation syndrome (HARS).

Purpose of the Study:

• To validate previously identified baboon candidate genes in humans exposed to radiation.
• To compare in vivo and ex vivo radiation exposure measurements across species.
• To establish dose-response relationships for gene expression changes.

Main Methods:

• Irradiated baboons and human patients (CT, radiotherapy, total-body irradiation) and analyzed blood samples.
• Cultivated and irradiated peripheral blood cells ex vivo from baboons and humans.
• Measured gene expression of candidate genes (WNT3, POU2AF1, CCR7, ARG2, CD177, WLS, FDXR, PCNA, DDB2) using qRT-PCR.

Main Results:

• Validated six baboon candidate genes in human leukemia patients.
• Observed an inverse expression pattern for FDXR between baboons and humans.
• Demonstrated that peripheral blood cells are radiation-responsive targets for WNT3 and POU2AF1.
• Confirmed linear dose-response relationships for FDXR, WNT3, and POU2AF1 in human ex vivo samples, correlating with in vivo data.

Conclusions:

• Six candidate genes identified in baboons were validated in humans for radiation exposure assessment.
• Ex vivo blood cell models can reliably estimate in vivo radiation doses across a wide range (0.001-5 Sv).
• Findings support the development of gene expression-based diagnostic tests for radiation incidents.