Gene expression profiles in human cells submitted to genotoxic stress

Area of Science:

• Molecular Biology
• Genetics
• Cellular Biology

Background:

• Cellular response to genotoxic agents is complex, involving DNA repair, cell cycle control, signal transduction, apoptosis, and oncogenesis.
• Understanding gene expression profiles is crucial for evaluating cellular responses to genotoxic stress.

Purpose of the Study:

• To document gene expression profiles in response to genotoxic agents (gamma-rays and cyclophosphamide).
• To analyze differential gene expression in lymphocytes from radiation-exposed individuals, a human fibroblast cell line, and cyclophosphamide-treated SLE patients.

Main Methods:

• Utilized cDNA arrays to analyze differential gene expression profiles.
• Examined lymphocytes from radiation workers, an in vitro irradiated human fibroblast cell line (VH16), and T lymphocytes from systemic lupus erythematosus (SLE) patients treated with cyclophosphamide.

Main Results:

• Ionizing radiation exposure induced genes associated with cell cycle regulation (TRRAP), DNA repair (Ligase IV), signal transduction (MAPK8IP1, MAPK10), apoptosis/tumorigenesis (RASSF2), and DNA damage response (p53).
• In vitro irradiation of VH16 cells showed complex molecular responses, including induction of apoptotic pathways, signaling, cell cycle arrest, and oxidative damage.
• Cyclophosphamide treatment in SLE patients induced 154 differentially expressed genes, including those involved in drug detoxification, cell cycle control, apoptosis, and tumor suppression, with evidence of induced apoptotic pathways (APAF1, cytochrome c).

Conclusions:

• Genotoxic stress triggers complex gene expression changes, impacting DNA repair, cell cycle, signaling, and apoptosis.
• Specific genes and pathways are modulated differently by ionizing radiation and cyclophosphamide.
• Findings provide insights into molecular mechanisms of cell response to genotoxic stress, relevant for basic and clinical research.