Host cell reactivation of cisplatin-treated adenovirus is reduced in nucleotide excision repair deficient mammalian cells and several human tumour cells.

Cisplatin is widely used for chemotherapy of a variety of human cancers. Cisplatin exerts its toxic effect by covalently binding to DNA, resulting in monofunctional adducts, intrastrand crosslinks, and interstrand crosslinks. Several recent reports suggest that the cellular capacity for DNA repair, especially nucleotide excision repair (NER), is an important determinant in the sensitivity of cells to cisplatin. We have used a sensitive host cell reactivation (HCR) technique to examine the repair capacity for cisplatin-damaged DNA in several different mammalian cell types. HCR of cisplatin-damaged adenovirus (Ad) was reduced in all UV-sensitive NER deficient Chinese hamster ovary (CHO) cells examined (complementation groups 1 to 6) compared to NER proficient CHO cells. HCR of cisplatin-damaged Ad was also reduced in fibroblasts from patients with xeroderma pigmentosum (XP) complementation groups A, B, C, D, F, and G compared to that in normal human fibroblasts. Differences in the HCR of cisplatin-treated Ad were also detected among human cancer cell lines, suggesting some tumour cells may be deficient in the NER of cisplatin-DNA adducts.