Cis dichlorodiammine platinum induced DNA interstrand cross-links in primary cultures of human ovarian cancer

Br J Cancer. 1991 Aug;64(2):288-92. doi: 10.1038/bjc.1991.293.

Abstract

We quantified and examined the kinetics of DNA interstrand cross links (DNA-ISC) caused by Cis dichlorodiammine platinum (DDP) using the method of alkaline elution in 58 highly purified human ovarian tumours growing in primary culture. A large heterogeneity in both the quantity and kinetics of DDP induced DNA-ISC was observed in cultures derived from neoplasms of different patients and from different lesions of the same patient. In the majority of cases. DNA-ISC lasted for prolonged time intervals after 1 h drug exposure, being significantly repaired only 48 or 72 h following drug washout. The persistence of DNA-ISC is probably due to a prolonged formation of these lesions for up to 24 h as assessed by the change in the repair kinetics that occurred after preventing new DNA-ISC formation by quenching of monoadducts with thiourea. The inefficient repair of DDP monoadducts appears therefore to be a possible reason for the permanence of DNA-ISC. These studies suggest that the long permanence of DNA-ISC in human ovarian cancer could be the basis for the high selectivity of DDP for this human malignancy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cisplatin / pharmacology*
  • Cross-Linking Reagents*
  • DNA Damage*
  • DNA Repair
  • Female
  • Humans
  • Kinetics
  • Ovarian Neoplasms / genetics*
  • Tumor Cells, Cultured

Substances

  • Cross-Linking Reagents
  • Cisplatin