Quenching of DNA:Platinum(ll) Monoadducts as a Possible Mechanism of Resistance to c/s-Diamminedichloroplatinum(ll) in L1210 Cells

A line of mouse leukemia L1210 cells resistant to c/'s-diamminedichloroplatinum(ll) (c/s-DDP)was compared with its parent cell line in order to determine whether the sensitivity difference could be related to DNA interstrand cross-linking as measured by the alkaline elution technique. The study was stimulated by a previous finding that the magnitude of DNA interstrand crosslinking, although somewhat reduced in this resistant line, did not account for the relatively high degree of resistance. Therefore, the kinetics of cross-link formation and removal was studied. Cross-link removal rates were determined by the use of thiourea to stop the delayed formation of interstrand cross-links from c/sDDP:DNA monoadducts. There was no significant difference between the cross-link removal rates in the parent and resistant lines. Computer-analyzed kinetics was consistent with an en hanced c/s-DDP:DNA monoadduct quenching mechanism in the resistant cells.