Analysis in vivo of antitumor activity, cytotoxicity and Interaction between plasmid DNA and the cis-dichloro-tetra-amine-ruthenium(III) chloride.
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.
Menezes
Carla Silva Rodrigues
CS
Instituto de Genética e Bioquímica, Universidade de Uberlândia, Av. Pará 1720, 38.400-902 Uberlândia, Brazil. casm_br@yahoo.com
de Paula Costa
Luiz Carlos Gebrim
LC
de Melo Rodrigues Avila
Veridiana
V
Ferreira
Márcio José
MJ
Vieira
Carlos Ueira
CU
Pavanin
Luis Alfredo
LA
Homsi-Brandeburgo
Maria Inês
MI
Hamaguchi
Amélia
A
de Paula Silveira-Lacerda
Elisângela
E
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
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D017975:Ruthenium Compounds; D003404:Creatinine; D006836:Hydro-Lyases; C045581:lactate dehydratase; D001663:Bilirubin