Genotoxic substances are highly dangerous chemicals that may cause DNA damage and even consequent in cancer. That is why exposure to genotoxins poses a great risk to all living organisms. Identifying the potential of a substance to cause harm to our genetic material is thus an important task for scientists. Many approaches in creating test systems for the detection of genotoxicity with different end points as read-outs have been made over the years. Due to the variety of genotoxic substances and their modes of action, challenges in the detection of those substances are inevitable. This thesis deals with the activity of p53 and the upregulation of its target genes, since p53 is activated as a response to DNA damage. Hence, a new p53 reporter cell line has been characterized and the results have been compared to other p53-depended assays. Additionally, the expression of the endogenous p53 target genes GADD45a and CDKN1a (p21) have been examined after genotoxic insults in the p53 competent cell lines HepG2 and HCT-116. Finally, a GADD45a-GFP knock-in using the CRISPR/Cas9 system in HepG2 cells has been generated as an approach of creating a novel GADD45a reporter cell line, which achieved an efficiency of 2.5 %.