Genotoxicity of platinum and palladium compounds in human and bacterial cells

Gebel, Thomas; Lantzsch, Heiko; Pleßow, Kirsten; Dunkelberg, H

doi:10.1016/s1383-5718(96)00145-3

Cited by 111 publications

(42 citation statements)

References 25 publications

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“…Antitumor platinum drugs induced intra-and interstrand cross-linking effects, chromosomal aberrations, SCE, and increased MN frequencies in a number of experimental systems in vitro and in vivo as well as in human cells [13,[31][32][33][34][35][36]. In addition, the activation of apoptotic cell death was described as a key defense mechanism by cisplatin to remove cells with severe DNA damage [26][27][28].…”

Section: Discussionmentioning

confidence: 99%

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Genotoxic Action of Cycloplatam, a New Platinum Antitumor Drug, on Mammalian Cells in vivo and in vitro

Nersesyan¹,

Perrone

Roggieri

et al. 2003

Chemotherapy

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Cycloplatam (CP), a new antitumor platinum compound of the second generation, was first synthesized in Russia. This drug shows less toxicity in vivo than the widely used cisplatin and carboplatin and a higher antitumor activity than carboplatin. CP is not nephrotoxic with respect to the platinum-based antitumor agents. CP is actually studied in clinical phase II trials in Russia and Armenia. Promising results were obtained in patients with lung, ovary, and prostate cancers. The aim of this work was to study the micronuclei (MN) inducing effect of CP in vivo in murine bone marrow cells and in human lymphocytes in vitro. The mutagenic activity of CP in bone marrow of mice was significantly lower than that of cisplatin at equitoxic doses. In human lymphocytes CP induced a dose-dependent increase of MN, beginning at a very low dose (0.1 µM). Our results showed that CP is much less toxic and MN inducing in vivo in murine bone marrow than cisplatin. In vitro data evidenced that CP is more toxic and genotoxic to human cells than cisplatin. The evidence of a MN-induced activity of an antitumor drug suggests a potential risk for long-time survivors.

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Section: Discussionmentioning

confidence: 99%

“…The genotoxicity of a large number of platinum antitumor compounds has been demonstrated in different experimental systems in vitro and in vivo [12][13][14][15][16][17].…”

Section: Introductionmentioning

confidence: 99%

Genotoxic Action of Cycloplatam, a New Platinum Antitumor Drug, on Mammalian Cells in vivo and in vitro

Nersesyan¹,

Perrone

Roggieri

et al. 2003

Chemotherapy

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“…The Pd compounds PdCl 2 , K 2 PdCl 4 , cis-Pd(NH 3 ) 2 I 2 , cisPd(NH 3 ) 4 Cl 2 , and the corresponding transPd compounds did also not show any genotoxicity in human lymphocytes. In contrast, different Rh compounds tested (e.g., RhCl 3 , K 2 RhCl 5 , (NH 4 ) 3 RhCl 6 ) were genotoxic in bacterial systems (Kanematsu et al 1980;LaVelle and Krause 1986;Bünger et al 1996;Gebel et al 1997;Lantzsch and Gebel 1997). In general, Pt and Rh compounds show stronger genotoxicity (likely mediated by oxidative damage induction of DNA) than do Pd salts (Migliore et al 2002).…”

Section: Genotoxicitymentioning

confidence: 96%

Platinum‐Group Metals

Hoppstock¹,

Sures²

2004

Elements and Their Compounds in the Environment

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“…However, when cis-DDP enters the cell as a neutral or dichloride complex, the low intracellular concentration of chloride (ca. 4 mM) permits hydrolysis or consecutive ligand exchange, resulting in the loss of chloride anions, thus forming the final mutagenic electrophilic DNA-reactive cation for subsequent interaction with cellular nucleophiles [Gebel et al, 1997]. Many cellular components that have nucleophilic sites such as DNA, RNA, proteins, membrane phospholipids, cytoskeletal microfilaments, and thiolcontaining molecules can react with cis-DDP.…”

Section: Cis-diamminedichloroplatinum(ii) (Cis-ddp)mentioning

confidence: 99%

Flavonoid compounds: a review of anticancer properties and interactions with cis‐diamminedichloroplatinum(II)

Kośmider¹,

Osiecka²

2004

Drug Development Research

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Flavonoid compounds, especially quercetin and genistein, have antitumor activity. These compounds are cytotoxic to cancer cells but have no or insignificant activity in normal cells. These beneficial properties prompted synthesis of flavonoid synthetic derivatives, e.g., flavopiridol; 5-amino-2,3-fluorophenyl)-6,8-difluoro-7-methyl-4H-1-benzopyran-4-one; B43-genistein and EGF-genistein). cis-DDP (cis-diamminedichloroplatinum(II)) is one of the most effective drugs used for chemotherapy, but its actions are limited by many side effects. Beneficial synergistic effects of flavonoids (e.g., quercetin, genistein, butein, tannic acid) and cis-DDP were found in cis-DDP-sensitive and resistant cancer cells that resulted in a lower toxicity for cis-DDP. Further studies focused on the synthesis of complexes of compounds belonging to different groups, e.g., cis-bis(3-aminoflavone)dichloroplatinum(II) where introduction of the flavone ligand altered the DNA-binding properties of the complex as compared to cis-DDP alone. The beneficial anticancer and antioxidant properties of flavonoids and their synthetic derivatives have prompted further research on the synergistic interactions of these compounds with routinely applied chemotherapeutic drugs, e.g. cis-DDP. Drug Dev.

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Genotoxicity of platinum and palladium compounds in human and bacterial cells

Cited by 111 publications

References 25 publications

Genotoxic Action of Cycloplatam, a New Platinum Antitumor Drug, on Mammalian Cells in vivo and in vitro

Genotoxic Action of Cycloplatam, a New Platinum Antitumor Drug, on Mammalian Cells in vivo and in vitro

Platinum‐Group Metals

Flavonoid compounds: a review of anticancer properties and interactions with cis‐diamminedichloroplatinum(II)

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