Intragenomic heterogeneity in DNA damage processing: Potential implications for risk assessment

We have documented three examples of heterogeneity in DNA repair in mammalian genomes. In African green monkey kidney cells certain bulky adducts are poorly repaired in the heterochromatic alpha DNA sequences relative to that in the bulk DNA. In Chinese hamster ovary cells an active ''housekeeping'' gene is proficiently repaired in a background of overall inefficient repair in the genome. In both of these cases the heterogeneity was illustrated in normal cells. In the third example, a hereditary defect in humans has been shown to cause a deficiency in DNA repair in some domains of the genome selectively. In this case the affected ''domains'' have yet to be identified and characterized, but our results so far indicate that an essential gene is poorly repaired in that system. 45 refs