Decomposition of Cisplatin in Aqueous Solutions Containing Chlorides by Ultrasonic Energy and Light

Macka, Mirek; Borák, J.; Seménková, L.; Kiss, František

doi:10.1002/jps.2600830611

Cited by 26 publications

(15 citation statements)

References 16 publications

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“…By contrast, excitation of the charge-transfer band (254 nm) results in redox chemistry. Cisplatin itself undergoes photosubstitution reactions, losing an ammine ligand when irradiated with 300-350 nm light (Macka et al, 1994). On the basis of this information, we propose that the mechanism of protein photo-cross-linking by cisplatin-modified DNA involves photosubstitution of one of the ligands by a protein residue, Lys-6 in the case of HMG domain B.…”

Section: Discussionmentioning

confidence: 99%

Photoreactivity of Platinum(II) in Cisplatin-Modified DNA Affords Specific Cross-Links to HMG Domain Proteins

Kane

Lippard

1996

Biochemistry

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Cisplatin-modified DNA forms specific complexes with proteins that contain the DNA binding motif known as the high-mobility group (HMG) domain. As a tool for investigating the role of these proteins in mediating the cytotoxic effects of cisplatin, a set of cisplatin analogs was prepared in which one of the ammine ligands was replaced with a photoreactive tethered aryl azide ligand. The ability of DNA modified by these platinum complexes to photo-cross-link to HMG1 was investigated. During this study, it was discovered that DNA modified with cisplatin itself can undergo photoinduced cross-linking to HMG1 when irradiated with 300 nm light. The covalent complexes resulting from this latter cross-linking reaction are completely reversed by the addition of sodium cyanide and can be degraded by proteinase K. These results confirm the presence of a protein-DNA cross-link and demonstrate that the platinum atom itself forms the point of attachment. By contrast, DNA modified with transdiamminedichloroplatinum(II), [Pt(dien)Cl]Cl, or [Pt(NH3)3Cl]Cl does not cross-link to HMG1 upon irradiation. The photochemistry was exploited to cross-link a 15-base pair oligonucleotide containing a single, site-specific cis-[Pt(NH3)2{d(GpG)-N7(1),-N7(2)}] intrastrand adduct to domain B of HMG1. Following proteolytic digestion of the resulting covalent complex, the site of attachment to the protein was determined by Edman degradation of the resulting peptide-DNA complex to be a single residue on HMG domain B, Lys-6. The data further suggest that this amino acid binds to platinum at a site made available by photolabilization of a purine ligand. These results afford the first structural information about the interaction of HMG domain proteins with cisplatin-modified DNA.

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Section: Discussionmentioning

confidence: 99%

Photoreactivity of Platinum(II) in Cisplatin-Modified DNA Affords Specific Cross-Links to HMG Domain Proteins

Kane

Lippard

1996

Biochemistry

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“…The biological activity of a cisplatin solution is determined by a number of critical variables in preparation, including the use of 0.9% NaCl as a solvent (Greene et al , 1979; Sigma-Aldrich, 2007), protection from light (Macka et al , 1994; Zieske et al , 1991), and the avoidance of the addition of DMSO (Fischer et al , 2008; Kerrison and Sadler, 1977; Sundquist et al , 1986). Mice received one cycle (a single cycle consisting of five consecutive daily ip injections followed by a 16-day recovery period) of 2.5 mg/kg/day, two cycles of 2.5 mg/kg/day, or one cycle of 5.0 mg/kg/day cisplatin followed by one cycle of an equivalent volume of PBS (Figure 1).…”

Section: Methodsmentioning

confidence: 99%

Cisplatin-induced alterations in the functional spermatogonial stem cell pool and niche in C57/BL/6J mice following a clinically relevant multi-cycle exposure

Harman¹,

Richburg²

2014

Toxicology Letters

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A typical clinical cis-diamminedichloroplatinum (II) (cisplatin) dosing regimen consists of repeated treatment cycles followed by a recovery period. While effective, this dosing structure results in a prolonged, often permanent, infertility in men. Spermatogonial stem cells (SSCs) are theoretically capable of repopulating the seminiferous tubules after exposure has ceased. We propose that an altered spermatogonial environment during recovery from the initial treatment cycle drives an increase in SSC mitotic cell activity, rendering the SSC pool increasingly susceptible to cisplatin-induced injury from subsequent cycles. To test this hypothesis, the undifferentiated spermatogonia population and niche of the adult mouse (C57/BL/6J) were examined during the recovery periods of a clinically-relevant cisplatin exposure paradigm. Histological examination revealed a disorganization of spermatogenesis correlating with the number of exposure cycles. Quantification of Terminal Deoxynucleotidyl Transferase-Mediated Digoxigenin-dUTP Nick End Labeling (TUNEL) staining indicated an increase in apoptotic frequency following exposure. Immunohistochemical examination of Foxo1 and incorporated BrdU showed an increase in the undifferentiated spermatogonial population and mitotic activity in the recovery period in mice exposed to one cycle, but not two cycles of cisplatin. Immunohistochemical investigation of glial cell line-derived neurotrophic factor (GDNF) revealed an increase in production along the basal Sertoli cell membrane throughout the recovery period in all treatment groups. Taken together, these data establish that the impact of cisplatin exposure on the functional stem cell pool and niche correlates with: (1) the number of dosing cycles; (2) mitotic activity of early germ cells; and (3) alterations in the basal Sertoli cell GDNF expression levels after cisplatin-induced testicular injury.

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“…These consisted of (1) two different incubation temperatures, that is, 37°C and 25°C, (2) incubation times varying from 40 minutes to 24 hours, and (3) molar ratios between Pt compounds and DNA varying from ratios 2 : 1 up to 200 : 1. DNA platination reactions were performed in the dark to inhibit photoaquation processes as aqueous solutions of cisplatin and carboplatin are degraded via illumination, especially at wavelengths below 500 nm [35, 36]. To terminate the reactions after a given incubation time, the solutions were passed through a gel filtration medium packed into a column.…”

Section: Methodsmentioning

confidence: 99%

DNA-Platinum Thin Films for Use in Chemoradiation Therapy Studies

Rezaee

Alizadeh

Hunting

et al. 2012

Bioinorganic Chemistry and Applications

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Dry films of platinum chemotherapeutic drugs covalently bound to plasmid DNA (Pt-DNA) represent a useful experimental model to investigate direct effects of radiation on DNA in close proximity to platinum chemotherapeutic agents, a situation of considerable relevance to understand the mechanisms underlying concomitant chemoradiation therapy. In the present paper we determine the optimum conditions for preparation of Pt-DNA films for use in irradiation experiments. Incubation conditions for DNA platination reactions have a substantial effect on the structure of Pt-DNA in the films. The quantity of Pt bound to DNA as a function of incubation time and temperature is measured by inductively coupled plasma mass spectroscopy. Our experiments indicate that chemical instability and damage to DNA in Pt-DNA samples increase when DNA platination occurs at 37°C for 24 hours, the condition which has been extensively used for in vitro studies. Platination of DNA for the formation of Pt-DNA films is optimal at room temperature for reaction times less than 2 hours. By increasing the concentration of Pt compounds relative to DNA and thus accelerating the rate of their mutual binding, it is possible to prepare Pt-DNA samples containing known concentrations of Pt while reducing DNA degradation caused by more lengthy procedures.

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Decomposition of Cisplatin in Aqueous Solutions Containing Chlorides by Ultrasonic Energy and Light

Cited by 26 publications

References 16 publications

Photoreactivity of Platinum(II) in Cisplatin-Modified DNA Affords Specific Cross-Links to HMG Domain Proteins

Photoreactivity of Platinum(II) in Cisplatin-Modified DNA Affords Specific Cross-Links to HMG Domain Proteins

Cisplatin-induced alterations in the functional spermatogonial stem cell pool and niche in C57/BL/6J mice following a clinically relevant multi-cycle exposure

DNA-Platinum Thin Films for Use in Chemoradiation Therapy Studies

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