Role of DNA damaging agents in the transformation of breast epithelial cells

Abstract

DNA is exposed to different damaging agents and prolonged exposure to these agents may lead to cancer. This study aims to understand the role of DNA damaging agents such as UV and Proflavine in transformation of breast epithelial cells. Previous studies form the lab showed that activation of DNA-PKcs upon MNU (N-Methyl-N-Nitrosourea) treatment leads to aberrant Golgi morphology. Alteration in Golgi morphology was observed upon UV induced DNA damage suggesting that this might be a characteristic feature of DNA damage. The other DNA damaging agent of interest, Proflavine is a DNA intercalator and is widely used as a topical antiseptic. Recent reports reveal that Proflavine can lead to frameshift mutations and has carcinogenic properties. Preliminary results from this study reveal that Proflavine can cause single stranded DNA breaks leading to DNA damage. Further experiments are required to identify the DNA damaging properties of Proflavine. Aberrant Golgi morphology and DNA–PKcs activation was also observed in Proflavine treated cells which further validate that damage induced altered Golgi phenotype is through the activation of DNA-PKcs.