The Role of DNA Damage and DNA-Damaging Environmental Chemicals in Carcinogenesis

Environmental pollutants have a strong impact on human health. It has been estimated that up to 90 per cent of all human cancers are due to exposure to chemical carcinogens. These chemicals fall mainly into the category of epigenetic or genotoxic carcinogens. The target of the genotoxic chemicals is clearly DNA. Reactive chemicals or metabolically produced intermediates bind covalently to DNA bases, and several nucleophilic substitution sites in DNA have been noted. The adduct formation in DNA is not a random process, when it is a question of bulky aromatic hydrocarbon like benzo[a]pyrene the process is highly stereoselective. The damage in DNA may be repaired efficiently and with high fidelity depending on the three-dimensional shape and location of adducts. However, if the repair fails for some reason, the DNA modified by the carcinogen may cause a mutation in cell replication. The mutation may bring about cell dysfunction which is the initiation phase of tumourigenesis. The challenge of the environmental exposure-related cancer studies are that the biological outcome is a result of the interaction of the exposure and genome of an individual. This underlines the supposition that gene-environment interactions are at the core of a specific disease outcome.