Genotoxic action of the sesquiterpene lactone centratherin on mammalian cells in vitro and in vivo.
Centratherin is a sesquiterpene lactone known for its antimicrobial, anti-inflammatory, and trypanocidal activities. The aim of this study was to determine the clastogenic and cytotoxic potential of centratherin in human lymphocytes and in mice. Human lymphocytes in culture were submitted to either continuous treatment or treatment during G(2) phase of the cell cycle. After continuous treatment the 0.2 microg/ml concentration induced a significant increase in total of chromosomal aberrations (CA) and sister chromatid exchange compared to control, and it reduced the mitotic index (MI). In the treatment during G(2) phase, centratherin induced a significant increase in the frequency of CA for all concentrations tested (0.1, 0.3, and 0.5 microg/ml). In the in vivo test system all three concentrations tested in mice (3.3, 6.7, and 13.3 mg/kg b.w.) induced a significant increase in CA compared to the negative control. On the basis of these results, centratherin showed clastogenic and cytotoxic activity on in vitro and in vivo mammalian systems.
Burim
R V
RV
Faculty of Medicine of Ribeirão Preto, São Paulo University, Ribeirão Preto, São Paulo, Brazil. revab@rgm.fmrp.usp.br
Canalle
R
R
Lopes
J L
JL
Vichnewski
W
W
Takahashi
C S
CS
D000818:Animals; D002478:Cells, Cultured; D002869:Chromosome Aberrations; D005260:Female; D016195:G2 Phase / Q000187:drug effects; D006801:Humans; D007783:Lactones / Q000633:toxicity; D008214:Lymphocytes / Q000187:drug effects / Q000648:ultrastructure; D008297:Male; D051379:Mice; D009153:Mutagens / Q000633:toxicity*; D012717:Sesquiterpenes / Q000633:toxicity*; D012854:Sister Chromatid Exchange / Q000187:drug effects
D007783:Lactones; D009153:Mutagens; D012717:Sesquiterpenes; C442701:centratherin