Pani B, Barbisin M, Russo E, Tamaro M, Baccichetti F, Carlassare F, Marzano C, Rodighiero P, Bordin F
Dipartimento di Biochimica, Biofisica e Chimica delle Macromolecole, Università di Trieste, Italy.
Mutat Res. 1994 Dec 1;311(2):277-85. doi: 10.1016/0027-5107(94)90186-4.
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).
已对4-羟甲基-4',5'-苯并补骨脂素（HMBP）损伤中国仓鼠卵巢细胞（CHO）DNA以及在体外抑制拓扑异构酶II活性的能力进行了研究。该化合物的特征是在补骨脂素分子的呋喃侧缩合有一个四环。与其他已知的呋喃香豆素衍生物相反，HMBP在没有UVA激活的情况下就能诱导哺乳动物细胞发生染色体畸变。通过碱性和中性洗脱法在CHO细胞中研究了HMBP在黑暗中诱导的DNA损伤；检测到相当数量的单链断裂、DNA-蛋白质交联以及双链断裂的形成。此外，在连环和解连环试验中，HMBP在体外似乎都能抑制哺乳动物拓扑异构酶II的活性。在这些实验中，该药物只有在与DNA底物预孵育时才有效。这些结果也与HMBP在黑暗中的细胞毒性和诱变活性一致，这已在中国仓鼠V79细胞（V79/HGPRT系统）上得到验证。
