title: Analysis in vivo of antitumor activity, cytotoxicity and Interaction between plasmid DNA and the cis-dichloro-tetra-amine-ruthenium(III) chloride.
abstract: Several metallic compounds recognized as potent antitumor agents, have been developed and tested in vivo and in vitro. In this work, we evaluated the toxic, therapeutic, and cytotoxic properties of the cis-dichloro-tetra-amine-ruthenium(III) chloride. Transplanted animals with Sarcoma 180 cells were treated with ruthenium(III) complex and injected i.p., at different time intervals. After the 15th day, tumoral postimplant, the animals were sacrificed and their lungs, kidneys, liver, and tumors were removed and processed for histopathological analysis. Blood samples were also taken for haematological and biochemical analyses. Interaction between the ruthenium complex and the DNA was also investigated. Besides being cytotoxic for the S180 cells, the metallic compound induced tumoral volume reduction and increased survival time of the animals treated. Serum levels of LDH, creatinine, and bilirubin increased, but no serious irreversible histopathological alterations were observed in the analyzed tissues. The compound did not cause anemia, but reduced the number of leukocytes in the treated animals. The absence of viable S180 cells, necrotic cells, and the presence of granulation tissue were observed in tumor tissue of treated animals. The Ru(III) complex, in the presence of the reduction agent, caused plasmid DNA to fragment. These results suggest that cis-RuCl(2)(NH(3))(4)Cl compound is a potent antitumoral drug in vitro and in vivo, which seems to involve binding to DNA molecule.
authors: Instituto de Genética e Bioquímica, Universidade de Uberlândia, Av. Pará 1720, 38.400-902 Uberlândia, Brazil. casm_br@yahoo.com
authors: Carla Silva Rodrigues
authors: CS
authors: Menezes
authors: Luiz Carlos Gebrim
authors: LC
authors: de Paula Costa
authors: Veridiana
authors: V
authors: de Melo Rodrigues Avila
authors: Márcio José
authors: MJ
authors: Ferreira
authors: Carlos Ueira
authors: CU
authors: Vieira
authors: Luis Alfredo
authors: LA
authors: Pavanin
authors: Maria Inês
authors: MI
authors: Homsi-Brandeburgo
authors: Amélia
authors: A
authors: Hamaguchi
authors: Elisângela
authors: E
authors: de Paula Silveira-Lacerda
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000633:toxicity; D001663:Bilirubin / Q000097:blood; D001772:Blood Cell Count; D003404:Creatinine / Q000097:blood; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D006651:Histocytochemistry; D006836:Hydro-Lyases / Q000097:blood; D020128:Inhibitory Concentration 50; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010957:Plasmids / Q000187:drug effects / Q000378:metabolism; D017975:Ruthenium Compounds / Q000494:pharmacology* / Q000633:toxicity; D012510:Sarcoma 180 / Q000097:blood / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D017975:Ruthenium Compounds; D003404:Creatinine; D006836:Hydro-Lyases; C045581:lactate dehydratase; D001663:Bilirubin