Platinum complexes inhibit repair of potentially lethal damage following bleomycin treatment

Abstract

The SCC-25 cell line is a well-established line derived from a human squamous carcinoma of the head and neck. The capacity of this cell line for recovery from potentially lethal damage following X-ray treatment has been documented. The survival curve of stationary phase SCC-25 cells exposed to various concentrations of bleomycin is biphasic with an initial sensitive phase and a less sensitive second phase as is common for many cell lines. Stationary phase SCC-25 cells were exposed to 100 mU ml-1 of bleomycin for 1 h. The drug was removed and the cells were allowed various periods to recover from potentially lethal damage. After 24 h, the SCC-25 cells showed a recovery ratio (R/R0) of 7.0 which corresponded to an immediate survival at a drug level of 27 mU ml-1, a dose 3.7-fold less than the exposure concentration of 100 mU ml-1. Over the course of the first 4 h following bleomycin exposure, 0.5 microM CDDP was a very effective inhibitor of potentially lethal damage repair, giving a R/R0 of 1.1 or nearly complete inhibition of recovery. Between 2 and 4 h the R/R0 was 1.6-1.8 with CDDP and 4.1-5.3 without CDDP indicating appreciable inhibition of recovery. Plant (10 microM) and Plato (10 microM) produced potentially lethal damage recovery inhibition patterns very similar to that of CDDP. After 1 h the recovery ratios in the presence of Plant and Plato were 1.1-1.3. Between 2 and 4 h, Plato and Plant gave recovery ratios of 1.8-2.3 and 1.6-1.9, respectively. NIPt and Pt(terpy) were examined at both 10 microM and 25 microM for their ability to inhibit potentially lethal damage recovery after bleomycin treatment. After 1 h, NIPt gave a recovery ratio of 1.3-1.4, and after 2-4 h the recovery ratio was 1.7-2.6. Pt(terpy) gave recovery ratios of 1.3-1.6 after 1 h and 1.5-1.8 after 24 h.