Corresponding Author: Denise C. Endringer - Universidade Vila Velha UVV - Rua Comissário José Dantas de Melo, 21 - Boa Vista - Vila Velha ES - CEP.29102-770 - tel.:27 3421-2072 - e-mail:denise.endringer@uvv. br ou endringe@gmail.com Revista de Ciências Farmacêuticas Básica e Aplicada Journal of Basic and Applied Pharmaceutical Sciences Rev Ciênc Farm Básica Apl., 2011;32(3):419-423 ISSN 1808-4532 Antimutagenic activity of Carica papaya L. assayed in vivo by micronucleus test Kalil, I.C. 1 ; Gibson, B.A.V. 1 ; Ribeiro, C.A. 1 ; Benincá, L.S. 1 ; Brasil, G.A. 1 ; Andrade, T.U. 1 ; Batitucci, M.C.P. 2 ; Endringer, D.C. 1* 1 Curso de Farmácia, Universidade Vila Velha - UVV 2 Universidade Federal do Espírito Santo – UFES Recebido 22/09/2011 / Aceito 17/11/2011 ABSTRACT There is little information about in vivo toxic effects of the ethanolic extract of leaves of Carica papaya L. (ECP). Therefore, in this study ECP was characterized chemically by HPLC-RP and the antimutagenic and cytotoxic activities of an aqueous solution of ECP (CA) were assessed by the micronucleus (MN) bioassay. The extract consisted mainly of polar substances, one of which was rutin. The MN test was performed on groups of Wistar rats, as follows: negative control (NC) - vehicle; positive control (CP40) - cyclophosphamide (40 mg/kg, ip), 24h; extract-treated (CA) - ECP (500 mg/kg, po), 24h; extract + cyclophosphamide-treated (CACP40) - ECP (500 mg/kg, po), 48, 36 and 24 h, plus cyclophosphamide (40 mg/kg, ip), 24h. The MN index was 3.2 ± 1.79 and 1.6 ± 0.5, for NC and CA, and the PCE-to-NCE ratio was 1.38 ± 0.52 and 1.13 ± 0.28, respectively, indicating low cytotoxicity of CA. CP40 showed a high MN index of 20 ± 4.9, but CACP40 only 3.0 ± 1.6, the same as NC, indicating an antimutagenic effect. The study suggests that ECP has low toxicity and possesses an antimutagenic protective effect in which rutin may be involved. Keywords: Carica papaya. HPLC-RP. Micronucleus bioassay. The use of medicinal plants to treat many diseases has been recorded in all regions of the world (WHO, 2000). The importance of popular knowledge about medicinal plants cannot be overestimated. However, their pharmacological properties and safety should be tested (WHO, 2000). The safety of either a synthetic drug or an herbal medicine may be assessed by several toxicological assays. The 50% lethal dose (LD 50 ), chronic toxicity, genotoxic effect and mutagenicity assays are the most frequently used (Paulo et al., 2009). The in vivo micronucleus (MN) assay, performed on mouse bone marrow erythrocytes, has been offcially used to evaluate damage caused by xenobiotic substances in the body (Schmid, 1976). The MN bioassay can be used to test the chemopreventive action of drugs, when the drug is given before the administration of the mutagenic agent (Salvadori et al., 2003). Chemopreventive agents are synthetic or natural substances that are used to inhibit, retard or reverse the carcinogenic process (Sporn & Suh, 2000). Cyclophosphamide is a cytotoxic drug that acts by alkylating DNA. The drug thus blocks DNA duplication completely, resulting in cell death, or incompletely, causing mutation (Vahlsing et al., 1977). The fruits of Carica papaya L., known as papaya or pawpaw, are widely consumed, worldwide and in Brazil (Castro & Anjos, 2008). l-Lycopene and benzylisothiocyanate (Rossetto et al., 2008) were isolated and identifed in the fruit of this species and α-tocoferol, carotenoid (Ching & Mohamed, 2001), lycopene (Breemen & Pajkovic, 2008) and favonoids (Miean & Mohamed, 2001) were identifed in the leaves of C. papaya. Several studies have evidenced the chemopreventive action of lycopene, favonoids and benzylisothiocyanate (Etherton- Kris et al., 2002; Ferrari & Torres, 2002; Kuroiwa et al., 2006). Biological activity has been reported in the stems, fruits and leaves of C. papaya, such as weak inhibition of angiotensin-converting enzyme (ACE), immunomodulation and cytotoxicity (Braga et al., 2007; Otsuki et al., 2010). Recently, the immunomodulatory and cytotoxic activities of an aqueous extract of C. papaya were detected in tumor cell and human peripheral blood cell lines (Otsuki et al., 2010). However, data have not been published about either the in vivo cytotoxic effect or the antimutagenic effect of C. papaya. Therefore, the aims of the present study were to characterize the ethanolic extract of C. papaya by chromatographic fngerprint analysis and assess its