Cisplatin carcinogen

Carcinogenicity. A number of metals have been shown to be carcinogenic in humans or animals. Arsenic, certain chromium compounds, and nickel are known human carcinogens beryllium, cadmium, and cisplatin are probable human carcinogens. The carcinogenic action, in some cases, is thought to result from the interaction of the metallic ions with DNA (see Chapter 11 for a detailed discussion of carcinogenesis). 

Cisplatin caused lung adenomas and skin papillomas in female mice and leukemia in rats. Animal carcinogen reasonably anticipated to be a human carcinogen.2... 

As stated in a recent review [53], the development of efficient cisplatin chemotherapy has brought an unexpected challenge as many patients survive longer, they find themselves at risk of late complication in their anti-neoplasic therapy. Indeed, although unambiguous data on the capacity of cisplatin to induce secondary cancers in humans is still lacking, its carcinogenic properties in rats and mice has been reported [53] [54], Treatment-... 

Oe Cisplatin. Cisplatin [civ-diammincdichloroplatinum(II)] is a clinically used chemotherapeutic agent in the treatment of a variety of human cancers. The anticancer activity of cisplatin is believed to result from cytotoxicity induced by cisplatin DNA adducts. Not surprisingly, cisplatin itself is a mutagen and carcinogen. G - T and A —> T transversions appear to be the main mutations induced by cisplatin. 

Greene MH. Is cisplatin a human carcinogen J Natl Cancer Inst 1992 84 306-12. 

Cisplatin caused azoospermia in humans within 2 months after initiation of treatment. Recovery of sperm counts occurred in most patients within 1-2 years after cessation of treatment. Cisplatin administered in combination with etopsoside is carcinogenic in humans. 

Antisera or monoclonal antibodies (MAbs) have been described that recognize DNA adducts formed by many carcinogens. With regard to anticancer drugs, antibodies have been described that recognize DNA modifications formed by methylating agents (1), cisplatin (2), and melphalan (3). 

Chibbee R and Oed MJ (1989) The mutagenic and carcinogenic properties of three second generation antitumour platinum compounds a comparison with cisplatin. Eur J Cancer Clin Oncol 25 27-33. 

Nickel(II) increases the sensitivity ofV79 Chinese hamster cells towards cisplatin and trans-platin by interference with distinct steps of DNA repair. Carcinogen 20 1177-1184. 

A to 1 with supporting evidence from other data relevant to the evaluation of carcinogenicity and its mechanisms) Etoposide [33419-42-0] in combination with cisplatin and bleomycin (Vol. 76 2000) Formaldehyde [50-00-0] (Vol. 88 in preparation)... 

A number of cytostatic drags, including cisplatin, are carcinogenic. NADH is able to protect cells from the carcinogenic effects of these chemotherapeutic agents. Hence ENADA, the stabilized oral form of NADH, may present a safe, nontoxic, biological supplement for prevention of cancer. 

The hypothesis of the 0-6 guanine Involvement does provide an extra bonus In that a mechanism of action can be postulated, and tested, which allows an explanation of the selective destruction of cancer cells. If the cancer cell becomes so because of its inability to repair the 0-6 guanine lesion caused by a carcinogen then it may also be unable to repair the cisplatin induced damage. But the normal cells have Intact repair mechanisms and can repair the damage prior to DNA replication and... 

Induction of poly(ADP-ribosyl)ation was reported in the kidney after in vivo application of renal carcinogens such as trichloroethene and dichloroacetylene subsequent to DNA double-strand breaks. Potassium bromate and ferric nitrilotriacetate, whose nephrotoxicity is thought to result from ROS formation, both induced poly(ADP-ribosyl)ation with the concomitant formation of DNA double-strand breaks. Recendy, PARP activation has been associated with both gentamicin and cisplatin-induced nephrotoxicity.Both types of nephrotoxicity involve the generation of ROS and the beneficial effects of different therapeutic approaches aimed at reducing ROS formation have been evaluated. 

Some cancer chemotherapeutic drugs are carcinogenic and/or mutagenic. They are widely used in hospital and laboratories, and there is a widespread demand for methods for their safe disposal and for surface decontamination, a field completely neglected. Research was therefore initiated on a number of these compounds doxorubicin, daunorubicin, methotrexate, dichlorom-ethotrexate, cyclophosphamide, ifosfamide, vincristine sulfate, vinblastine sulfate, 6-thioguanine, 6-mer-captopurine, cisplatin, lomustine, chlorozotocin, streptozotocin, carmustine, semustine, PCNU and melphalan. 

Since free platinum intercalates or intracalates in DNA, cisplatin can be cytotoxic towards lung cancer cells, but it can also enhance carcinogenicity in experimental animals (Leopold et al. 1981). (-)-Epigallocatechin gallate can prevent cisplatin-induced lung tumorigenesis in A/J mice (Mimoto et al. 2000). 

The inertness snggests the reason that Mo is the only essential transition metal fonnd in biological systems that is not a first-row transition metal. Most second- and third-row transition metals appear to be too strongly bound and inert to engage in metabolic processes (Hoeschele et al. 1991). However, the inertness of some second- and third-row elements, such as Pt(II), can be useful for the chemotherapeutic activity of these complexes. The inertness probably plays a role also in the mutagenicity and mild carcinogenicity observed for cisplatin and the mutagenicity of other inert complexes, especially Cr(III) complexes. 

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