Revival: Biological Effects of Low Level Exposures to Chemical and Radiation (1992)

CHAPTER 3

DNA Repair: As Influenced by Age, Nutrition,

and Exposure to Toxic Substances

Ronald Hart, Ming Chou, Ritchie Feuers, Julian Leakey, Peter Duffy,

Beverly Lyn-Cook, Jack Lipman, Kenji Nakamura, Angelo Turturro,

and William Allaben, National Center for Toxicological Research,

Jefferson, Arkansas

INTRODUCTION

A critical component in assessing the effect of low-level exposure to
toxicants is the repair of a genome that may be damaged by the agent.
Because the adverse effect of many low-level toxicants is below practical
observable thresholds, models are necessary to extrapolate the observable
effects to realistic levels.1 In these models, those agents that work through
damaging the genome are usually considered to have irreversible effects —
often a consequence of the procedure, which extrapolates from doses of
agent that can often overwhelm cellular defenses and cause some toxic
damage.2 At low levels of agent, the normal processes of cellular defense
and protection of genomic integrity are likely to be intact, influencing the
response to a toxin. One of the most important factors in the protection of
genomic integrity is DNA repair. The term actually covers a multitude of
activities. We will concentrate on excision repair, which directly reverses the
effects of a toxicant binding to the DNA.
Just as DNA repair modulates the response of a genome to an insult,
DNA repair is itself modulated by a number of environmental factors.
Among the important modulators of DNA repair are age, nutrition, and
toxicants themselves.

AGE

Although there have been many attempts to address the effect of aging on
different aspects of DNA repair, many studies are difficult to interpret.
Some use cells kept in vitro (with questionable relevance to in vivo aging);

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