Cis dichlorodiammine platinum induced DNA interstrand cross-links in primary cultures of human ovarian cancer.
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.
Balconi
G
G
Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
Pang
Y
Y
Broggini
M
M
Morali
F
F
Marzola
M
M
Erba
E
E
Ponti
M
M
Spinelli
L
L
Mangioni
C
C
Redaelli
L
L
D002945:Cisplatin / Q000494:pharmacology*; D003432:Cross-Linking Reagents; D004249:DNA Damage; D004260:DNA Repair; D005260:Female; D006801:Humans; D007700:Kinetics; D010051:Ovarian Neoplasms / Q000235:genetics*; D014407:Tumor Cells, Cultured
D003432:Cross-Linking Reagents; D002945:Cisplatin