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OLIVEIRA, R. C. S. Assessment of Cytotoxicity, genotoxicity and mutagenicity of cassava (Manihot esculenta Crantz) in HepG2 cells. 2012. 100f. Thesis (Doctoral). Faculdade de Ciências Farmacêuticas de Ribeirão Preto – Universidade de São Paulo, Ribeirão Preto, 2012. The food factor can be considered a tumor causing agent responsible for the etiology of gastric cancer in the state of Pará. Cassava (Manihot esculenta Crants) is one of the many food species of the Amazon indiscriminately consumed by the inhabitants of the northern region. Cyanide, its main toxic component, can be released during cassava processing through the hydrolysis of the cyanogenic glycoside linamarin. In the body, cyanide blocks the electron transport chain by inhibiting cell respiration which brings about, among other things, the production of free radicals which can act upon DNA through the formation of exocyclical adducts. The main goal of this study was the assessment of the citotoxic, genotoxic and mutagenic role of the leaves and tucupi juice of wild and sweet cassava, both raw and cooked, using the MTT, comet and cytome assays in HepG2 cells. The results gathered have shown that cell viability decreases as the concentration increases in most treatment groups. In the comet assay, a visual analysis has shown that potassium cyanide, used as a standard, was genotoxic in all concentrations tested (5.0, 15.0 and 25.0 μg/mL). Samples of wild cassava leaves were genotoxic only in concentrations of 15.0 and 25.0 μg/mL for raw leaves, and 5.0, 15.0 and 25.0 μg/mL for cooked leaves. Samples of sweet cassava leaves were genotoxic only when cooked (5.0 and 25.0 μg/mL). Yet, samples of tucupi juice, both raw and cooked, have shown damage to DNA in HepG2 cells at all concentrations tested (20.0, 40.0 and 60.0 μg/mL). In performing DNA fragmentation analysis, it was observed that potassium cyanide was genotoxic only in the assessment of percentage DNA in tail. Whereas the wild and sweet cassava samples, in a general fashion, have shown greater values of percentage DNA in tail, tail moment and olive moment than the negative control group, but only the cassava leaves revealed statistically significant values, in some concentrations. For the cytome assay, concentrations of leaves and of tucupi juice, raw and cooked, of both wild and sweet cassava, have shown a slight increase in the number of micronuclei in binucleated HepG2 cells, not statistically significant as compared to the negative control group. On the other hand, the number of nucleoplasmic bridges and nuclear buds in binucleated cells was lower than the value found in the negative control group. The damages verified herein by the comet assay may be transiently present as intermediates formed during repair of DNA lesions. The absence of

Avaliação da citotoxicidade, genotoxicidade e mutagenicidade da mandioca (Manihot esculenta Crantz) em célula tumoral HepG2