Mechanisms of DNA damage and repair: Implications for carcinogenesis and risk assessment

This book is based on the papers presented at the conference on ''Mechanisms of DNA Damage and Repair: Implications for Carcinogenesis and Risk Assessment,'' held at the National Bureau of Standards on June 2-7, 1985. This volume deals with mechanisms of DNA damage and repair at the molecular level; consequences of unrepaired or misrepaired damage, with major emphasis on carcinogenesis; drugs which bind selectively to altered and potentially damaging DNA sequences; and potential utilization of DNA damage as an endpoint for assessing risks of uv light, ionizing radiations, chemicals, drugs, and hazardous agents in foods. Because the induction of mutations by radiation and genotoxic chemicals has been observed to follow one-hit kinetics in some instances, it is generally assumed that any level of exposure to a DNA-damaging agent may increase the risk of genetic disease or cancer in an exposed population. At the same time, however, there is evidence that although the DNA of living cells is continually damaged by natural background radiation, free radicals, and other naturally occurring processes, most of the damage is normally repaired. Knowledge of the intricate relationships between the toxicity of hazardous agents and the level of exposure, possible synergistic effects of exposure to other agents, damage to DNA and its repair or misrepair, repair capacity of the affected cells, and the factors influencing the processes of damage and repair at various stages in their evolution are essential for understanding molecular carcinogenesis and for developing scientifically based risk assessment