Scientific Publications by FDA Staff

Int J Toxicol 1983 Jan-Feb;2(1):7-17

Interspecies Differences in the Removal of DNA Adducts

Hart RW, Chang MJW

Numerous physical and chemical agents damage cellular DNA in vivo. Such damage has been associated with various biochemical, physiological, and pathological dysfunctions including: alterations in gene expression, cell death, mutation, birth defects, cancer, and aging. Cells and organisms unable to prevent the induction of DNA damage or to repair such damage once it is induced, are predisposed to one or more of these pathologies. Over the course of evolution, living systems have developed various mechanisms to cope with such damage including enzymatic repair, information redundancy and, in extreme situations, cellular replacement. Enzymatic repair can be divided into two general categories: prereplication and post-replication repair. Each of these categories includes many ¿repair¿ systems which differ with the size of the repaired region, the nature of the enzymes involved in the repair process, the type of agent inducing the repair process or form of lesion removed. Over the last decade, numerous methods have been developed to measure DNA damage, both directly as well as indirectly, but few studies exist comparing the results of these methods with one another. Little is known as to whether these methods are measuring the same or different endpoints. Interspecies, intertissue, and interorgan comparisons can only be made when comparable techniques have been utilized. From such studies, it is now apparent that significant differences in DNA repair exist among species, within species, and between organs. Further, it is now a reasonable speculation that such differences may, in part, account for differences in organ susceptibility and risk per cell per unit time for spontaneous malignant transformation observed between species.