Repair of DNA interstrand crosslinks after busulphan. A possible mode of resistance

The technique of alkaline elution has been used to study the interaction between the antineoplastic drug busulphan and the DNA of cells derived from the transplantable rodent Yoshida sarcoma. A dose-dependent proteinase-resistant filter retention was observed after drug treatment, which indicated the presence of DNA interstrand cross-links. Such cross-links were removed after 6 h in cells resistant to busulphan but not in the busulphan-sensitive parent cells, even after 24 h. Such temporal differences in DNA cross-linking could be correlated with cell survival and also with the level of anaphase chromosome aberrations, which was found to be four-fold higher in the sensitive line than in the resistant line.