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THE INFLUENCE OF DNA REPAIR PROCESSES ON CANCER RISK ASSESSMENT AT LOW EXPOSURE LEVELS
Citation:
Preston, R J. THE INFLUENCE OF DNA REPAIR PROCESSES ON CANCER RISK ASSESSMENT AT LOW EXPOSURE LEVELS. Presented at 2000 Conf. on Topics in Toxicology & Risk Assessment, Approaches for the 21 Century, Kings Island, Ohio, 4/10-13/2000.
Description:
The process of cancer risk assessment is deemed currently to allow for the inclusion of mechanistic data to help establish the nature of the tumor response curve at low exposure levels of environmental chemical carcinogens. For the present discussion, cancer is a genetic disease, characterized by a high level of genomic instability that aids in the progression through several steps from a normal cell to a metastatic tumor. The production of the mutations necessary for this progression occurs via errors ofDNA replication and/or DNA repair. For the majority of chemicals, mutations are produced by replication errors. The relative frequency of induced mutations is a consequence of the outcome of the race between DNA repair and DNA replication; the more repair prior to replication the lower the mutation frequency. Different classes of DNA lesions are repaired by different repair processes; all of which have the aim of returning the DNA to its predamaged state, or at least to one not resulting in phenotypic change. The various repair processes have different kinetics and degrees of fidelity and so the level of induced mutagenesis will be a feature of initial lesion type. In addition, the characteristics of DNA repair might vary with exposure level, i.e. level ofDNA damage. Experimental systems are being developed to assess these potential variables to the mutagenic process. The information developed for DNA repair will have great utility for predicting tumor responses at low exposure levels, particularly in the understanding of overall probability of converting an induced DNA damage into a mutation.
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