Question

Dis uss the different types of DNA damage that can promote cancer. Be sure to discuss the effects of this damage on the cells and how the cancer cells begin to grow. Discuss how different physical agents (such as chemicals or radiation) cause DNA damage that contribute to cancer.

Answer 1

Oxidative DNA damage refers to the oxidation of specific bases. 8-hydroxydeoxyguanosine (8-OHdG) is the most common marker for oxidative DNA damage and can be measured in virtually any species. It is formed and enhanced most often by chemical carcinogens.

Hydrolytic DNA damage involves deamination or the total removal of individual bases. Loss of DNA bases, known as AP (apurinic/apyrimidinic) sites, can be particularly mutagenic and if left unrepaired they can inhibit transcription. Hydrolytic damage may result from the biochemical reactions of various metabolites as well as the overabundance of reactive oxygen species.

Ultraviolet and other types of radiation can damage DNA in the form of DNA strand breaks. This involves a cut in one or both DNA strands; double-strand breaks are especially dangerous and can be mutagenic, since they can potentially affect the expression of multiple genes. UV-induced damage can also result in the production of pyrimidine dimers, where covalent cross-links occur in cytosine and thymine residues. The most common pyrimidine dimers are cyclobutane pyrimidine dimers (CPD) and pyrimidine (6-4) pyrimidone photoproducts (6-4PP). CPD and 6-4PP are the most frequent DNA mutations found in the p53 protein in skin cancers. Pyrimidine dimerscan disrupt polymerases and prevent proper replication of DNA.

DNA damage may also result from exposure to polycyclic aromatic hydrocarbons (PAHs). PAHs are potent, ubiquitous atmospheric pollutants commonly associated with oil, coal, cigarette smoke, and automobile exhaust fumes. A common marker for DNA damage due to PAHs is Benzo(a)pyrene diol epoxide (BPDE). BPDE is found to be very reactive, and known to bind covalently to proteins, lipids, and guanine residues of DNA to produce BPDE adducts. If left unrepaired, BPDE-DNA adducts may lead to permanent mutations resulting in cell transformation and ultimately tumor development.