ResumoA leucemia linfóide aguda (LLA) é uma neoplasia hematológica heterogênea, caracterizada por uma disfunção das células tronco da medula óssea, que leva a uma proliferação clonal desordenada das células precursoras de origem linfóide. Ocorre principalmente na infância em crianças entre 2 e 5 anos de idade. Embora a causa da LLA seja desconhecida, é improvável que a transformação leucêmica seja resultante de um fato isolado, mas sim do acúmulo de múltiplos processos envolvendo interações complexas quanto à susceptibilidade do hospedeiro. Apesar de apresentar um alto percentual de cura, trata-se de uma doença rapidamente progressiva, que carece de urgência no tratamento para um melhor prognóstico e sobrevida dos pacientes, deve-se sempre obter um diagnostico precoce e diferencial, que deve conter características específicas da LLA, podendo assim, distingui-la das demais patologias que contém os sinais e sintomas compatíveis com os da LLA, como a mononucleose infecciosa e anemia aplásica. Isso só é possível com uma investigação clínica e laboratorial adequada, e com exames específicos, tais como, mielograma, imunofenotipagem, exames citoquímicos e citogenéticos. Estes exames permitem a classificação morfológica da LLA, além de diferenciar os diversos estágios de maturação das células e as anormalidades cromossômicas, possibilitando assim a qualificação dos pacientes em diferentes grupos de risco, sendo fundamental para determinar o tratamento adequado para cada caso. A demora do diagnóstico acarreta atraso no tratamento, o que diminui significantemente a sobrevida e/ou cura dos pacientes infanto-juvenis. Por este e outros pontos, o diagnostico diferencial tem seu lugar de destaque no prognostico da LLA. Descritores: Diagnóstico, leucemia linfocítica aguda, câncer infantil, mielograma.

Punicalagin is the major ellagitannin constituent from leaves of Lafoensia pacari, a Brazilian medicinal plant widely used for the treatment of peptic ulcer and wound healing. Genotoxic, cytotoxic, antigenotoxic, and anticytotoxic effects of punicalagin were assessed using micronucleus (MN) test and comet assay in mice. Due to the extensive use of L. pacari in the wound healing process, we also assessed the angiogenic activity of punicalagin using the chick chorioallantoic membrane (CAM) angiogenic assay. The highest dose of punicalagin (50mg/kg) showed significant cytotoxic effect by MN test and in the co-treatment with cyclophosphamide (CPA), this cytotoxicity was enhanced. Co-treatment, pre-treatment and post-treatment of punicalagin with CPA led to a significant reduction in the number of DNA breaks and in the frequency of CPA-induced MN, indicating antigenotoxic effect. Using the CAM model, punicalagin exhibited angiogenic activity in all doses mainly at the lowest concentration (12.5μg/μL). Therefore, these findings indicate an effective chemopreventive role of punicalagin and a high capacity to induce DNA repair. Also, the angiogenic activity presented by punicalagin in this study could contribute for the processes of tissue repairing and wound healing.

Commonly used guidelines for the management of human immunodeficiency virus (HIV) infection (highly active antiretroviral therapy, HAART) include drug combinations such as tenofovir disoproxil fumarate (TDF) + lamivudine (3TC) and combivir [zidovudine (AZT) + 3TC] + efavirenz (EFV). These combinations may enhance the genotoxic effects induced by such drugs individually, since the therapy requires lifelong adherence and the drugs have unknown effects during treatment. Thus, the evaluation of the benefits and risks of HAART is of great importance. In order to assess the cytotoxic and genotoxic potential of three concentrations of each of the antiretroviral combinations TDF + 3TC (800 + 400, 1600 + 800, and 3200 + 1600 mg/kg body weight, BW) and combivir + EFV (200 + 100 + 400, 400 + 200 + 800, and 800 + 400 + 1600 mg/kg BW) after two exposure periods (24 h and 48 h), in the present study the in vivo comet assay (single-cell gel electrophoresis) and the mouse bone marrow micronucleus test were used. Neither TDF + 3TC nor combivir + EFV induced DNA damage at any concentrations tested after 24 h or 48 h using the comet assay. After 24 h, both combinations increased the micronucleus frequency at all concentrations tested. After 48 h, combivir + EFV increased the micronucleated polychromatic erythrocyte (MNPCE) frequency at the two highest concentrations tested. Polychromatic erythrocytes (PCE)/normochromatic erythrocytes (NCE) ratio was high for both combinations, suggesting that they can be mitogenic. Since genotoxicity may be related to carcinogenesis, it is necessary to conduct further studies to verify the long-term mutagenic effects of these drugs.

ABSTRACT. Salacia crassifolia (Mart. Ex. Schult.) G. Don., popularly known in Brazil as "bacupari", "cascudo", and "saputá", is a shrub of the Celastraceae family that is unique to the Brazilian Cerrado region. In folk medicine, this plant has been mainly used to treat skin cancer and gastric ulcers. In the present study, the genotoxic, cytotoxic, antigenotoxic, and anticytotoxic effects of S. crassifolia stem bark fractions (hexane, ethyl acetate, and hydroalcoholic extracts) were evaluated using the mouse bone marrow micronucleus test. Our results showed that none of the S. crassifolia fractions led to a significant increase in the frequency of micronucleated polychromatic erythrocytes (MNPCE) (P > 0.05), suggesting the absence of genotoxicity. In the antigenotoxicity assessment, a significant decrease in the MNPCE frequency was observed in all fractions of this plant (P < 0.05), demonstrating its protective action against genotoxicity induced by mitomycin C (MMC), which was used as the positive control. Only the hexane fraction of S. crassifolia significantly decreased the poly-and normochromatic erythrocyte ratio (PCE/NCE) in all doses tested (P < 0.05), demonstrating its cytotoxic activity. In association with MMC, both ethyl acetate and hydroalcoholic fractions significantly increased the PCE/NCE ratio in almost all doses tested (P < 0.05), demonstrating the protective action of S. crassifolia against the cytotoxic effect of the positive control. In contrast, the hexane fraction presented a significant decrease in the PCE/NCE ratio in all treatments (P < 0.05), demonstrating an increase in this plant's cytotoxicity in mouse bone marrow cells.

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Therefore, GD showed relevant antigenotoxic, anticytotoxic and cytotoxic effects, which indicate that it may be a probable candidate for chemoprevention or for the development of new cancer therapies.

The aim of this study was to evaluate the possible protective of C. guianensis oil against MMC and CP, which are direct-and indirect-acting chemical mutagens, using the micronucleus test. Three experiments were performed. First the C. guianensis oil was co-administered to mice at doses of 250, 500 and 1000 mg/ kg bw with 4 mg/kg bw MMC or 50 mg/kg bw CP. Second, the mutagenic drug (CP) was administered ip 50 mg/kg bw and after 6 and 12 hours 250 and 500 mg/kg bw of C. guianensis oil were administered. In the last, C. guianensis oil was administrated (250 and 500 mg/kg bw) during five days and after it was administered ip 50 mg/kg bw CP. The results obtained showed that the C. guianensis oil is not cytotoxic neither genotoxic to mouse bone marrow. Regarding the antimutagenic effect, all doses of C. guianensis oil were significantly (p < 0.05) effective in reducing the frequency of micronucleated polychromatic erythrocytes, when compared with MMC or CP alone. Based on these results, our results suggest that the C. guianensis oil shows medicinal potential as an antimutagenic agent, modulating the mutagenicity caused by both direct-and indirect-acting chemical mutagens, in a mammalian model.

Salacia crassifolia (Mart. Ex. Schult.) G. Don. is a bush which belongs to Celastraceae family and occurs specially in Brazilian Cerrado. Its leaves, stem, seeds and fruits are popularly used for several medicinal purposes, such as antitumoral, antirheumatic, anti-inflammatory and antimicrobial. In this study, the mutagenic and antimutagenic activities of S. crassifolia stem bark fractions (hexane, ethyl acetate and hydroalcoholic) were evaluated by the Ames mutagenicity assay in Salmonella typhimurium TA98 and TA100 strains. By the obtained results, all S. crassifolia fractions did not significantly increase the number of prototrophic revertants for histidine (His + ) in both S. typhimurium strains tested (p > 0.05), suggesting absence of mutagenicity. Regarding antimutagenicity, the fractions ethyl acetate and hydroalcoholic significantly decreased the number of His + revertants colonies induced by positive control for strain TA98 (p < 0.05), demonstrating protection against mutagenicity induced by 4-nitroquinolile1-oxide, whereas the hexane fraction did not show antimutagenic effect in this strain. In the TA100 strain, all fractions of S. crassifolia protected DNA against the harmful action of sodium azide, and the hexane fraction exhibited the greatest protection in this work. Thus, it's possible conclude that the fractions of S. crassifolia tested in this study could be used in chemoprevention.Keywords: Salacia crassifolia, stem bark fractions, ames test, absence of mutagenicity, antimutagenicity. + induzidas pelo controle positive para a cepa TA98 (p < 0.05), demonstrando sua ação protetora contra a mutagenicidade induzida por 4-nitroquinolile1-oxide, enquanto a fração hexânica não demonstrou efeito antimutagênico nesta cepa. Na cepa TA100, todas as frações de S. crassifolia protegeram o DNA contra a ação lesiva de azida sódica, e a fração hexânica exibiu a maior proteção desse trabalho. Assim, concluímos que as frações de S. crassifolia testadas neste estudo poderiam ser utilizadas em quimioprevenção. Mutagenicitade e antimutagenicidade dePalavras-chave: Salacia crassifólia, frações da casca do caule, teste de ames, ausência de mutagenicidade, antimutagenicidade.