BINDING ACTIVITIES OF CIS-PLATIN-DAMAGE-RECOGNITION PROTEINS IN HUMAN TUMOR-CELL LINES

Proteins can be detected by South-western analyses of human tumour-cell extracts binding to double-stranded oligonucleotide DNA treated in vitro with the chemotherapeutic drug cis-diamminedichloroplatinum (II) (CDDP), but not to untreated DNA. The relative molecular masses of proteins binding to the CDDP-treated double-stranded oligonucleotide are 25, 48 and 97 kDa. The binding activity of 2 of the CDDP-damage-recognition proteins, of relative molecular mass 48 and 97 kDa, is greater in a CDDP-resistant human ovarian tumour cell line than in the parental sensitive line. South-western analysis of a panel of human bladder cell lines and CDDP-sensitive testicular cell lines show consistent patterns of CDDP-damage-recognition proteins within each cell type, however with differences between the 2 cell types. Binding of the proteins to CDDP-damaged DNA and the altered binding activity detected in tumour cell lines suggests that alteration in damage-recognition proteins could play a role in tumour response to CDDP.