Resumo: Não disponível. / Abstract: Diuron [3-(3,4-dichlorophenyl)-1,1-dimethyl urea] is a herbicide with carcinogenic activity in rats and mice which have developed respectively urothelial and mammary gland tumors in long-term studies. Accordingly, diuron has been categorized as a "likely human carcinogen" by the USEPA. Although the carcinogenesis initiating activity of diuron has been reported in an early initiation-promotion mouse skin study, its genotoxic potential has been disputed. It is necessary to clarify the mode of action through which it has caused rodent neoplasia and verify its relevance to humans. Herein, two experiments were developed to verify the initiating and promoting potentials of diuron in a 23- and a 21-week long mouse skin carcinogenesis protocol. In one, dimethylsulphoxide (DMSO) was the solvent for the herbicide; in the other, acetone was the alternative solvent in order to verify if DMSO had inhibitory influence on a potential cutaneous carcinogenic activity. The adopted schedule for the tumor promoting agent 12-O-tetradecanoylphorbol 13-acetate (TPA) resulted in skin ulcers, evidencing the need for careful selection of TPA dose levels and frequency of application in this model. In both studies diuron did not exert any influence on the skin carcinogenesis process, in contrast with results already reported in the literature. / Orientador: João Lauro Viana de Carmargo / Coorientador: Deilson Elgui de Oliveira / Banca: Maria Lucia Zaidan Dagli / Banca: Heidge Fukumasu / Mestre

Resumo: Não disponível. / Abstract: Not available. / Orientador: Luís Fernando Barbisan / Coorientador: João Lauro Viana de Camargo / Banca: Antonio Carlos Alessi / Banca: Ione Pellegatti Lemonica / Banca: Danielle Palma de Oliveira / Banca: Helenice de Souza Spinosa / Doutor

Orientador: Maria Luiza Cotrim Sartor de Oliveira / Banca: Carlos Márcio Nóbrega de Jesus / Banca: Heidge Fukumasu / Não disponível / Abstract: Diuron [3-(3,4-dichlorophenyl)-1,1-dimethylurea] is a herbicide that in a previous longterm study with Wistar rats fed at 2,500 ppm concentration showed high incidence of urothelial tumors in both genders. Accordingly, USEPA categorized Diuron as a "known/likely" human carcinogen. The accepted non-genotoxic mode of action (MOA) of Diuron encompasses urothelial necrosis induced by direct cytotoxicity, followed by regenerative cell proliferation and sustained urothelial hyperplasia that may favor neoplasia development. Scanning electron microscopy (SEM), light microscopy and labeling index are essentials tools for identification and classification of cytotoxic and proliferative changes in the bladder. The present study evaluated the dose-response of Diuron regarding urothelial lesions. Sixty male Wistar rats were fed Diuron for 20 weeks mixed in the diet at 0, 60, 125, 500, 1,250, or 2,500 ppm. Simple hyperplasia was significantly increased in the Diuron 1,250 and 2,500 ppm groups, and the cell proliferation at 2,500 ppm group. By SEM, the incidences and severity of lesions were significantly greater in the 500 and 1,250 ppm. Although numerically increased, the incidence of lesions in the 2,500 ppm group did not differ significantly from the control. The present study documented a doseresponse influence of Diuron on the rat urothelium, with a no observed effect level (NOEL) of 125 ppm. / Mestre

Orientador: Eleni Gomes / Banca: Mirna Helena Regali Seleghim / Banca: Eduardo Alves de Almeida / Resumo: Os basidiomicetos são conhecidos por sua capacidade em degradar a madeira. Essa característica deve-se à sua habilidade em oxidar a lignina presente nas plantas. Essa molécula é um composto recalcitrante formado por sub-unidades de fenilpropanóides e as enzimas capazes de degradá-la são conhecidas conjuntamente como enzimas ligninolíticas. Tais enzimas são inespecíficas. Essa característica confere-lhes o seu emprego na oxidação de compostos que possuem estrutura molecular semelhante à da lignina, tais como pesticidas e hidrocarbonetos poli-aromáticos, que possuem anéis aromáticos em sua estrutura. Dessa forma, é possível utilizar tais enzimas na degradação desses xenobióticos. Alguns basidiomicetos possuem a habilidade de crescer em meio com baixa atividade de água. Assim, é possível usá-los em processos de biorremediação de ambientes que possuem uma alta concentração de solutos, como em meios com alta salinidade. Esse trabalho teve como objetivo o estudo da capacidade de crescimento em meio líquido agitado com baixa atividade de água do basidiomiceto Dacryopinax elegans SXS323, promovida pela adição de cloreto de sódio 0,5 M, manitol 0,5 M ou glicerol 0,5 M ao meio de cultura; a produção de enzimas ligninolíticas e o seu poder de degradação do herbicida diurom nessas condições. Verificou-se que o basidiomiceto foi capaz de crescer sob todos os meios testados, sendo este mais pronunciado quando manitol ou glicerol foram acrescentados ao meio, averiguando-se um estímulo de crescimento. O manitol e o glicerol serviram como fonte secundária de carbono. O cloreto de sódio inibiu seu crescimento. Outro fator de inibição do crescimento foi a adição de diurom. A produção de enzimas ligninolíticas foi muito baixa, com pico de atividade de 3,67 U . L -1 com 144 horas de cultivo em meio com glicerol 0,5M. Apesar disso, detectou-se degradação... (Resumo comp'leto, clicar acesso eletrônico abaixo) / Abstract: The basidiomycetes are known for their ability to degrade wood. This feature is due to its ability to oxidize lignin of plants. This molecule is a compound formed by recalcitrant sub-units of phenylpropanoids and enzymes able to degrade it and are known as ligninolytic enzymes. These enzymes are nonspecific. This characteristic provides them the capability of oxidation of compounds that have molecular structures similar to lignin, such as pesticides and polyaromatic hydrocarbons, which possess aromatic rings in their structure. Thus, it is possible to use such enzymes in the degradation of xenobiotics. Some basidiomycetes have their ability to grow in media with low water activity. Thus, it can be used in bioremediation process in environments that have a high concentration of solutes, such as hypersaline environments. This work aimed to study the capability of the basidiomycete Dacryopinax elegans SXS323 to grow in liquid shaken with low water activity, promoted by the addition of sodium chloride 0.5 M, mannitol 0.5 M or glycerol 0.5 M to the medium culture, the production of ligninolytic enzymes and their degradation capability of the herbicide diuron in these conditions. It was found that the basidiomycete was able to grow in all media tested. The growth was most pronounced when mannitol or glycerol was added to the medium, probably working as a stimulus for growth, and were used as a secondary source of carbon. Sodium chloride inhibited its growth. Another factor inhibiting the growth was the addition of diuron. The ligninolytic enzyme production was very low, with peak activity of 3.67 U. L -1 with 144 hours in medium with glycerol 0.5 M. Nevertheless, we detected the degradation of the herbicide, registering 32.63% (glycerol 0.5 M, 192 hours), 25.47% (mannitol 0.5 M, 192 hours) 20.51% of reduction in medium with glucose 5.0 g . L -1 (240 hours)... (Complete abstract click electronic access below) / Mestre