Type II Guanine Oxidation Photoinduced by the Antibacterial Fluoroquinolone Rufloxacin in Isolated DNA and in 2'-Deoxyguanosine
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- 作者：Alessandra Belvedere ; Francisco Boscá ; Alfio Catalfo ; Maria C. Cuquerella ; Guido de Guidi ; and Miguel A. Miranda
- 刊名：Chemical Research in Toxicology
- 出版年：2002
- 出版时间：September 2002
- 年：2002
- 卷：15
- 期：9
- 页码：1142 - 1149
- 全文大小：141K
- 年卷期：v.15,no.9(September 2002)
- ISSN：1520-5010
文摘
The role played by type I (radical) and type II (singlet oxygen) mechanisms in the Rufloxacin(RFX)-photoinduced production of 8-hydroxy-2'-deoxyguanosine in DNA has been evaluated.This fluoroquinolone drug has been shown to be able to photoinduce increased levels of someDNA base oxidation products, such as 8-OH-dGuo, that are indicative of mutagenic andcarcinogenic events, with probable implications in aging processes. The relative weight of thetwo photosensitization mechanisms was obtained via determination of two different photoproducts of 2'-deoxyguanosine (dGuo), which are diagnostic of the two different pathways,namely, (4R*)- and (4S*)-4,8-dihydro-4-hydroxy-8-oxo-2'-deoxyguanosine and 2,2-diamino-4-[(2-deoxy-
fchars/beta2.gif" BORDER=0 ALIGN="middle">-D-erythro-pentofuranosyl)amino]-2,5-dihydrooxazol-5-one. The observed predominance of type II reaction is in agreement with the fact that the triplet state of RFX is able totransfer with high efficiency its energy to molecular oxygen, giving rise to singlet oxygen.Photophysical measurements suggest that hydrated electrons produced by Rufloxacin photoionization react with dGuo, Thd, and DNA, whereas these biomolecules quench the RFX tripletstate with low efficiency. Static quenching of Rufloxacin fluorescence indicates an interactionof this drug both with DNA and with dGuo. On the basis of these experimental data, Rufloxacinphotosensitization of DNA is proposed to occur by a type II mechanism.
fchars/beta2.gif" BORDER=0 ALIGN="middle">-D-erythro-pentofuranosyl)amino]-2,5-dihydrooxazol-5-one. The observed predominance of type II reaction is in agreement with the fact that the triplet state of RFX is able totransfer with high efficiency its energy to molecular oxygen, giving rise to singlet oxygen.Photophysical measurements suggest that hydrated electrons produced by Rufloxacin photoionization react with dGuo, Thd, and DNA, whereas these biomolecules quench the RFX tripletstate with low efficiency. Static quenching of Rufloxacin fluorescence indicates an interactionof this drug both with DNA and with dGuo. On the basis of these experimental data, Rufloxacinphotosensitization of DNA is proposed to occur by a type II mechanism.