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

G. Balconi, Y. Pang, M. Broggini, F. Morali, M. Marzola, E. Erba, M. L. Ponti Spinelli, C. Mangioni, L. Redaelli, F. Bertolero, M. D'Incalci

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)288-292
Number of pages5
JournalBritish Journal of Cancer
Volume64
Issue number2
Publication statusPublished - 1991

    Fingerprint

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Balconi, G., Pang, Y., Broggini, M., Morali, F., Marzola, M., Erba, E., Ponti Spinelli, M. L., Mangioni, C., Redaelli, L., Bertolero, F., & D'Incalci, M. (1991). Cis dichlorodiammine platinum induced DNA interstrand cross-links in primary cultures of human ovarian cancer. British Journal of Cancer, 64(2), 288-292.