This unit conducts work on the clinical and molecular parameters of resistance to platinum compounds and other DNA damaging agents. Work is being performed using fresh human materials, and established cell lines of malignant and non-malignant origin. Project Description: DNA Damage/Repair in Malignant and Non-Malignant Cell Lines: DNA damage and repair have been studied in three ways: studies of total genomic cellular repair of platinum-DNA adduct; studies of gene specific repair of platinum-DNA adduct; and studies of the repair of platinum-damaged plasmid DNA which has been transfected into target cells. Our studies of total genomic repair in human ovarian cancer cells and in non-malignant human leukocyte cell lines, show that DNA repair appears to the primary determinant of cisplatin resistance in both settings. In collaboration with Vilhelm Bohr of LMP/DCT/NCI, we have shown that differences in gene specific repair are even more pronounced than differences in total genomic repair, when comparing sensitive and resistant human ovarian cancer cells. Studies of transfected platinum-damaged plasmid into human leukocyte cell lines, show that T cells appear to be an excellent target for the study of interindividual differences in in vivo DNA repair capability. In contrast, B cells and other non-T cells are not as useful.
