Multiple effects of 3-aminobenzamide on DNA damage induced by cisplatin (DDP) in DDP-sensitive and -resistant rat ovarian tumor cell lines

Abstract

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 of 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.