Multiple effects of 3-aminobenzamide on DNA damage induced by cisplatin (DDP) in DDP-sensitive and -resistant rat ovarian tumor cell lines.
To investigate the mechanisms by which 3-aminobenzamide (3AB) reverses cisplatin (DDP) resistance in a rat ovarian tumor cell line, the effects of 3AB on DDP-induced DNA damage and repair were kinetically determined over a post-exposure period of 48 h. DNA single strand breaks (SSB) occurred maximally 12 h and 24 h following DDP exposure in DDP-resistant (O-342/DDP) and -sensitive (O-342) rat ovarian tumor cells, respectively. 3AB, present during and after the exposure, significantly increased SSB formation by DDP at 24 h (P < 0.02) and 48 h (P < 0.01) in O-342/DDP cells. To a lesser extent (P > 0.05), a similar tendency was also observed in O-342 cells. Formation of DNA interstrand cross-links (ISCL) by DDP reached a maximum by 12 h in either O-342 or O-342/DDP cells, but in the resistant cells they were both much lower and more rapidly removed. 3AB decreased ISCL in the sensitive cells at 12 h and thereafter with a maximum at 24 h (P < 0.05), while in the resistant cells the same treatment decreased ISCL at 12 h, had no effect at 24 h and increased ISCL at 48 h following DDP treatment. Therefore, it is concluded that 3AB has multiple effects on DNA damage and repair induced by DDP in both cell lines and increase of DNA-ISCL by 3AB at 48 h after the exposure in O-342/DDP cells might be related to its chemosensitizing effect in this line.
Chen
G
G
Institute of Toxicology and Chemotherapy, German Cancer Research Center, Heidelberg.
Zeller
W J
WJ
D000818:Animals; D001549:Benzamides / Q000494:pharmacology*; D002945:Cisplatin / Q000494:pharmacology*; D004247:DNA / Q000187:drug effects*; D004249:DNA Damage / Q000187:drug effects*; D004351:Drug Resistance; D005260:Female; D010051:Ovarian Neoplasms / Q000473:pathology*; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D051381:Rats; D014407:Tumor Cells, Cultured / Q000187:drug effects
D001549:Benzamides; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; C025160:3-aminobenzamide; D004247:DNA; D002945:Cisplatin