Chemical, Physical, and Genetic Factors Interfering with DNA Repair-a Review

Abstract

Because of its function as transmitter of genetic information, DNA is the most important macromolecule in need of protection from attack by chemical and physical agents, but mechanisms have evolved for repairing such damage to DNA. The presence of the adaptive response and other cellular repair systems (excision, post-replication, SOS, etc.) diminishes the toxicologic effects of low doses of toxic or muta-genic substances. Whether or not these genotoxic effects can be reduced to undetectable levels is not certain. Nonetheless, this repair-mediated diminution of damage due to chemicals constitutes one of the arguments in favor of existence of “safe” threshold levels of chemical exposure (Schendel, 1981). In turn, the repair process itself may be affected by chemical and physical agents. To determine the mode of action of a specific compound on the process of DNA repair becomes complex when all factors are taken into consideration. There are agents which interfere with DNA repair but they are also as active or more active in suppressing replicative DNA synthesis, as well as RNA and protein synthesis. The interference with repair may arise from other major processes such as alteration of energy metabolism and effects on precursor pathways and/or enzymatic cofactors. Whether or not an agent can specifically inhibit DNA repair enzymes has not been answered. The point must be made, however, that this type of interference with essential protective mechanisms is taking place and it may change anticipated outcomes of chemical or physical exposures. The magnitude of this effect due to the exposure of people to so many chemicals should be recognized and studied for their degree of interference with all the processes of DNA repair.