Assessment of Homologous Recombination System Gene Expression in Chemologically Induced Carcinogenesis In Vivo Models

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Homologous recombination (HR) system integrity is crucial for preventing genomic instability and malignant transformation.
• Dysfunction of HR genes, such as BRCA1 and BRCA2, is linked to aggressive tumor development.
• Chemical carcinogens provide models to study tumor formation and cellular adaptation to genotoxic stress.

Purpose of the Study:

• To investigate the expression of key homologous recombination system genes in a mouse model of chemically induced carcinogenesis.
• To evaluate the impact of 3-methylcholanthrene (MC) and trichloroacetic acid (TCA) on tumor formation and HR gene expression.

Main Methods:

• Chemically induced carcinogenesis model using ICR mice treated with MC or TCA.
• Histological analysis for tumor identification and characterization.
• RT-PCR, microarray analysis, and digital PCR for assessing gene expression and chromosomal aberrations (e.g., Brca1 deletions).

Main Results:

• Tumor formation observed two months post-MC treatment, characterized by pleomorphic cell morphology.
• Significant Brca1 deletions (60%) found in tumor samples.
• Hypoexpression of 14 genes, including Rad50, Rad51, Brca1, Brca2, and Pold4, was observed in tumors compared to normal tissue.
• Increased expression of Rad52 and Bard1 noted, with a correlation between increasing tumor mass and HR gene hypoexpression.

Conclusions:

• MC and TCA exposure influence tumor formation, with HR gene suppression potentially contributing to the process.
• Tumor progression is associated with declining DNA repair gene expression and accumulating aberrant gene states.
• Studying DNA repair gene status is vital for developing effective cancer diagnostic and therapeutic strategies.