Characterization of DNA damage induced by 3,4-estrone-o-quinone in human cells.
The DNA damage induced in a human breast cancer cell line treated with 1,5 (10)-estradiene-3,4,17-trione (3,4-estrone-o-quinone; 3,4-EQ) has been measured qualitatively and quantitatively. Single-strand (ss) but not double-strand (ds) DNA breaks were formed in MCF-7 cells treated with 3,4-EQ. The ss DNA breaks formed in MCF-7 cells were partially repaired after incubation of cells in 3,4-EQ-free media for 2 and 4 h (i.e. 33 and 23% repair, respectively, as compared to the ss DNA breaks in cells after a 1-h exposure to 3,4-EQ without a recovery period). The formation of interstrand DNA cross-links was demonstrated in MCF-7 cells exposed to the bifunctional alkylating agent, mitomycin C, but not in those exposed to 3,4-EQ. Protein-linked DNA breaks were detected in MCF-7 cells after exposure to camptothecin and etoposide but not 3,4-EQ, suggesting that the ss DNA breaks induced by 3,4-EQ are unlikely to be mediated via topoisomerases. The induction of ss DNA breaks was detected in the estrogen receptor-negative cell line, BT-20, after exposure to 3,4-EQ. Furthermore, excess estradiol in culture media did not prevent 3,4-EQ-induced ss DNA breaks, suggesting that the DNA damage was not mediated via the estrogen receptor. Evaluation of the newly synthesized quinone analogue, 5,6,7,8-tetrahydro-1-2-naphthoquinone, in the ss DNA breakage assay revealed that the A and B ring moiety of 3,4-EQ is sufficient to produce ss DNA breaks in MCF-7 cells.
Nutter
L M
LM
Department of Pharmacology, University of Minnesota, Minneapolis 55455.
Ngo
E O
EO
Abul-Hajj
Y J
YJ
D001943:Breast Neoplasms; D003432:Cross-Linking Reagents; D004247:DNA / Q000187:drug effects*; D004249:DNA Damage; D004260:DNA Repair; D004264:DNA Topoisomerases, Type I / Q000378:metabolism; D004277:DNA, Single-Stranded / Q000187:drug effects; D004963:Estrenes / Q000494:pharmacology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D015394:Molecular Structure; D011960:Receptors, Estrogen / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects
D003432:Cross-Linking Reagents; D004277:DNA, Single-Stranded; D004963:Estrenes; D011960:Receptors, Estrogen; C044208:1,5(10)-estradiene-3,4,17-trione; D004247:DNA; D004264:DNA Topoisomerases, Type I