Lack of correlation between repair of DNA interstrand cross-links and differential sensitivity of G(0) and proliferating CD4(+) lymphocytes towards cisplatin

G(0) cells in a tumor are insensitive to the chemotherapeutical agents. The nature of this resistance is nor completely understood. One of the factors modulating sensitivity of cells may he DNA repair of drug induced DNA dama ge. In this study we have compared gene-specific formation and repair of ci splatin-induced interstrand cross-links (ICL) in human Go and proliferating CD4(+) lymphocytes. Cisplatin killing of G(0)CD(4+) lymphocytes is ineffic ient, and these cells resemble those in a tumor. After exposure to cisplati n under similar conditions, the frequency of ICL introduced is twice as hig h in the proliferating compared to the resting lymphocytes. Repair of ICL w as measured in the housekeeping gene, dihydrofolate reductase (DHFR), in th e proliferation inducible c-myc gene, and in the inactive delta-globin gene . We observed similar relative rates and extent of ICL repair in all three genes studied, in G(0) or proliferating CD4+ lymphocytes. The mechanisms re sponsible for the resistance of G(0) CD4+ lymphocytes towards cisplatin are discussed.