we now show that beta-lapachone ( a ) activates the dna-unwinding activity of topoisomerase i , ( b ) inhibits the fast component of potentially lethal damage repair ( pldr ) carried out by hep-2 cells when present during or immediately following x-irradiation , ( c ) specifically and synergistically enhances the cytotoxic effects of dna-damaging agents which induce dna strand incisions , such as neocarzinostatin or x-rays , against a radioresistant human malignant melanoma ( u1-mel ) cell line , ( d ) does not synergistically potentiate melphalan-induced lethality against u1-mel cells but inhibits survival recovery and increases sister chromatid exchanges , and ( e ) does not further enhance the lethal effects of x-rays following prolonged drug exposures , indicating that beta-lapachone modifies initially created dna lesions or inhibits lesion repair but does not create lethal lesions by itself . beta-lapachone accelerated the dna-unwinding activity of topoisomerase i derived from avian erythrocytes , calf thymus , or hep-2 cells . beta-lapachone did not intercalate into dna , nor did it inhibit topoisomerase ii or ligation carried out by mammalian or t4 dna ligases .
C0037211
sister chromatid
C0007634
cells