## Exogenous sources of DNA damage

In addition to endogenous (internal) sources of damage, DNA damage can also be triggered by exogenous factors, which can be divided into three main groups: physical, chemical, and biological. Physical factors that cause DNA damage include UV and ionising radiation. Chemical factors that damage DNA form a very large group of substances – including those that are used in industry and agriculture, as well as some that are used in medicine. An example of such a substance is cisplatin, which leads to the formation of interchain crosslinks (Figure 5.2). If a crosslink is present, it blocks DNA replication. It is for this reason that cisplatin is used as a chemotherapeutic agent, as it prevents rapidly dividing tumour cells from replicating. In addition, some chemical substances that occur in the environment are in the form of pro-mutagens, which are inactive by themselves but become mutagens when activated following cell metabolism. These substances include polycyclic aromatic hydrocarbons, which are formed in the lungs as intermediates from the chemicals inhaled from cigarette smoke. Biological factors also have mutagenic potential, such as mobile genetic elements (transposons) and some viruses. These have the ability to insert themselves at any location in the genome, and if they integrate into a gene region, the gene is disrupted and produces a truncated protein with altered properties.

DNA damage occurs relatively frequently in cells - some sources report 10,000-20,000 occurrences of damage per cell per day. In some cases, this damage results in mutations (mutagenic effect), while in others, the damage blocks replication and transcription (cytotoxic effect). It is therefore not surprising that the cell has evolved several mechanisms over the course of evolution to remove such damage.