DNA damage and topoisomerase II inhibition induced by a benzopsoralen derivative.
The ability of 4-hydroxymethyl-4',5'-benzopsoralen (HMBP) to damage DNA of Chinese hamster ovary cells (CHO) and to inhibit the activity of topoisomerase II in vitro has been studied. This compound is characterized by a fourth ring condensed at the furan-side in the psoralen molecule. Contrary to other known furocoumarin derivatives, HMBP induces chromosomal aberrations in mammalian cells without UVA activation. The lesions induced in the dark by HMBP in DNA were studied by alkaline and neutral elution in CHO cells; comparable amounts of single-strand breaks and DNA-protein cross-links as well as the formation of double-strand breaks were detected. Moreover, HMBP appeared to inhibit the activity of mammalian topoisomerase II in vitro, in both the catenation and the decatenation assay. In these experiments the drug was effective only when it was pre-incubated with DNA substrate. These results are also consistent with the cytotoxic and mutagenic activity of HMBP in the dark, as tested on V79 Chinese hamster cells (V79/HGPRT system).
Pani
B
B
Dipartimento di Biochimica, Biofisica e Chimica delle Macromolecole, Università di Trieste, Italy.
Barbisin
M
M
Russo
E
E
Tamaro
M
M
Baccichetti
F
F
Carlassare
F
F
Marzano
C
C
Rodighiero
P
P
Bordin
F
F
D000818:Animals; D016466:CHO Cells / Q000187:drug effects / Q000201:enzymology; D006224:Cricetinae; D003412:Cricetulus; D003432:Cross-Linking Reagents; D018736:DNA Adducts; D004249:DNA Damage; D003624:Darkness; D011564:Furocoumarins / Q000737:chemistry / Q000633:toxicity*; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D012044:Regression Analysis; D059005:Topoisomerase II Inhibitors
C090414:4-hydroxymethyl-4',5'-benzopsoralen; D003432:Cross-Linking Reagents; D018736:DNA Adducts; D011564:Furocoumarins; D009153:Mutagens; D059005:Topoisomerase II Inhibitors; C056465:psoralen-DNA adduct