ISPO

Published in Cancer Detection and Prevention 2000; 24(Supplement 1).

Genotoxic action of the sesquiterpene lactone centratherin on mammalian cells in vitro and in vivo

RV Burim MSc, R Canalle MSc 1, JLC Lopes PhD 2, W Vichnewski PhD 2, CS Takahashi PhD 1

1 Faculty of Medicine of Ribeirão Preto, São Paulo University, Ribeirão Preto, SP, 2 Faculty of Pharmaceutical Sciences of Ribeirão Preto, São Paulo University, Ribeirão Preto, SP, 3 Faculty of Philosophy, Sciences and Letters of Ribeirão Preto, São Paulo University, Ribeirão Preto, SP, revab@rgm.fmrp.usp.br

AIMS: Centratherin (CTN) is a sesquiterpene lactone known for its antimicrobial, anti-inflammatory and trypanocidal activities. Since the acceptance of a new substance for medical use requires data about its toxicity, the aim of the present study was to determine the clastogenic and cytotoxic potential of CTN using in vitro and in vivo tests. METHODS: Human lymphocytes in culture were submitted to either continuous treatment or treatment during the G2 phase of the cell cycle. Chomosomal aberrations (CA), mitotic index (MI), sister chromatid exchange (SCE) and proliferation index (PI) were analyzed during continuous treatment, whereas only CA and MI were analyzed during G2 treatment. Three concentrations of CTN were tested for continuous treatment (0.05, 0.1 and 0.2 µg/ml) and for G2 treatment (0.1, 0.3 and 0.5 µg/ml). RESULTS: In the continuous treatment the 0.2 µg/ml concentration induced a significant increase in total number of CA and SCE compared to control, and reduced the MI. In the treatment during the G2 phase, CTN induced a significant increase in the frequency of CA for all concentrations tested, but did not change the MI. CA and MI were analyzed in the in vivo test system. CTN injected intraperitoneally in mice caused death at concentrations of 16.7 mg/kg bw or higher. All three concentrations tested in mice (3.3, 6.7 and 13.3mg/kg bw) induced a significant increase in CA compared to the negative control. CONCLUSIONS: Thus, we suggest that, under the experimental conditions of the present study, CTN showed clastogenic and cytotoxic activity on in vitro and in vivo mammalian systems.

KEY WORDS: natural products, genotoxicity, human lymphocytes, mice.

For more information, contact revab@rgm.fmrp.usp.br

Paper presented at the International Symposium on Impact of Biotechnology on Cancer Diagnostic & Prognostic Indicators; Geneva, Switzerland; October 28 - 31, 2000; in the section on genetic risk assessment.

http://www.cancerprev.org/Journal/Issues/24/101/303/3237