published_or_final_version / abstract / toc / Molecular Biology / Master / Master of Philosophy

Thesis (Ph. D.)--Northeastern University, 2008. / Title from title page (viewed Mar. 3, 2009). Graduate School of Arts and Sciences, Dept. of Chemistry and Chemical Biology. Includes bibliographical references (p. 156-170).

Thesis (Ph. D.)--University of Hong Kong, 2008. / Includes bibliographical references (leaves 207-242) Also available in print.

Thesis (Ph. D.)--University of Hong Kong, 2008. / Includes bibliographical references (leaves 207-242) Also available online.

Thesis (Ph. D.)--University of Hong Kong, 2000. / Includes bibliographical references (leaves vii, 276-309).

Thesis (Ph. D.)--University of Texas at Austin, 1998. / Vita. Includes bibliographical references (leaves 174-206). Available also in a digital version from Dissertation Abstracts.

Thesis (Ph.D.)--University of Hong Kong, 2000. / Includes bibliographical references (leaves vii, 276-309) Also available in print.

Thesis (M.S.)--University of Wisconsin--Madison. / Typescript. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 95-96).

Thesis (Ph. D.)--University of Texas at Austin, 2005. / Vita. Includes bibliographical references.

Made available in DSpace on 2014-06-11T19:27:55Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-02-23Bitstream added on 2014-06-13T19:15:37Z : No. of bitstreams: 1 solano_mlm_me_botfm.pdf: 545110 bytes, checksum: 986b5e538847b821da94872a1a03a326 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / Toxicam / Um ensaio de média-duração em múltiplos órgãos de roedores, baseado no paradigma iniciação-promoção da carcinogênese, foi proposto por pesquisadores japoneses como alternativa ao ensaio convencional de longaduração para detecção de cancerígenos químicos. Esse ensaio alternativo, denominado DMBDD (acrônimo para os 5 agentes iniciadores da carcingênese neste protocolo), foi originalmente padronizado com a linhagem de ratos Fischer 344. Em 1996, o IBAMA adotou oficialmente uma variação (DMBDDb), proposta por nosso laboratório, como fonte de evidência do potencial cancerígeno de praguicidas agrícolas. O protocolo adotado pelo IBAMA tem algumas particularidades, como o uso de ambos os gêneros de ratos da linhagem Wistar e dois grupos controle positivo (tratados com fenobarbital - FB ou com 2’-acetoaminofluoreno -2’-AAF). Este protocolo foi utilizado ao longo de seis anos em nosso laboratório (TOXICAN) para a realização de cinco bioensaios sob contratos com empresas do setor agroquímico. O presente estudo consiste da revisão dos diagnósticos de três órgãos desses ensaios - o fígado, rins e intestinos - escolhidos porque foram os que apresentaram mais lesões na análise de cada um daqueles ensaios. A capacidade indutora enzimática dos agentes do protocolo foi avaliada pela expressão imunohistoquímica das enzimas hepáticas CYP 2B1/2B2 e 1A2. Os resultados indicam atividade promotora do FB, embora menos evidente que a do 2’-AAF, particularmente nos ratos machos. Apesar da alta variabilidade da linhagem de rato Wistar , este estudo permitiu estabelecer um banco de informações sobre as lesões que caracteristicamente são encontradas naqueles órgãos dos animais Wistar submetidos ao protocolo DMBDDb. / A medium-term multi-organ rat bioassay based on the initiation-promotion carcinogenesis paradigm has been proposed by Japanese researchers as an alternative to the conventional long-term assay for chemical carcinogenesis detection. This alternative bioassay, designated DMBDD (after the five carcinogenic initiators of this protocol), was originally standardized with the male Fischer 344 strain of rats. In 1996, the Brazilian Agency for the Environment (IBAMA) officially recognized a variation (DMBDDb), proposed by our laboratory, as a valid source of evidence of the carcinogenic potential of agrochemicals. The protocol adopted by IBAMA has some modifications, such as the use of both sexes of the Wistar strain of rats and two positive controls (Phenobarbital – PB, 2’-acetoaminofluorene - 2’-AAF). During six years, five different bioassays managed under contract with agrochemical companies were developed by our laboratory (TOXICAN). This study presents the revised results obtained from three organs of this protocol – liver, kidney and intestines –, chosen because they most frequently presented lesions through those assays analyses. Besides, the induction of the CYP 2B1/2B2, 1A2 isoforms was also immunohistochemically evaluated in the liver. Our results document the promoting activity of PB, otherwise less evident than 2’-AAF, especially in male rats. Although a high variability of the Wistar rat strain tested was evident, this study allowed building up a data bank of characteristic lesions in those selected organs of Wistar rats under the DMBDDb protocol treatment.