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Agriculture pesticides as risk factor: toxicologic pathology, immunology, and molecular and analytical evaluations in experimental models of single or combined exposures


This research proposal aims to explore the problem of agriculture pesticides toxicity and its potential relevance to human health. Rats and mice orally (diet) exposed to pesticides will be used as models. This proposal will focus on two general topics and comprises seven (07) different studies. The first topic deals with the effects of extended exposure to five pesticides mixed at low concentrations. Residues of these pesticides were found by the Brazilian Agência Nacional de Vigilância Sanitária (ANVISA) in tomatoes regularly available for the Brazilian population. This mixture of pesticides will be verified regarding: 1) its potential for induction of the liver CYP450 enzyme system; 2) its promoting potential in a medium-term liver bioassay for carcinogenesis and 3) its potential for endocrine disruption in the young adult male rat. The other topic refers to Diuron, a widely used herbicide for sugar cane and soy cultures in Brazil. This herbicide has been shown to induce urinary bladder cancer in rats and has been considered a likely human carcinogen by the U.S. Environrnental Protection Agency (EPA). Under this topic, it will be verified: 1) the carcinogenic mode of action (MOA) of Diuron on the urothelial mucosa of rats, 2) its potential immunotoxicity to rats and 3) its initiating and promoting potentials in a mouse initiation promotion skin cancer model. The procedures to be developed encompass routine optical microscopy, immunohistochernistry, Westem-blot, real time PCR, serum hormones determination and assays for spermatic morph-functional integrity, and scanning electron rnicroscopy. Studies for improvement and validation of chemical analytical methods for the pesticides studied will also fie developed under each topic. (AU)

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Scientific publications (8)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
FERRUCIO, BIANCA; DA SILVA FRANCHI, CARLA ADRIENE; BOLDRIN, NATALIA FERREIRA; COTRIM SARTOR DE OLIVEIRA, MARIA LUIZA; VIANA DE CAMARGO, JOAO LAURO. Evaluation of Diuron (3-[3,4-dichlorophenyl]-1,1-dimethyl urea) in a Two-stage Mouse Skin Carcinogenesis Assay. TOXICOLOGIC PATHOLOGY, v. 38, n. 5, p. 756-764, . (06/60506-1, 08/01809-0)
FERRAGUT CARDOSO, ANA PAULA; IHLASEH CATALANO, SHADIA MUHAMMAD; DA ROCHA, MITSCHELI SANCHES; NASCIMENTO E PONTES, MERIELEN GARCIA; VIANA DE CAMARGO, JOAO LAURO; COTRIM SARTOR DE OLIVEIRA, MARIA LUIZA. Dose-response of diuron [3-(3,4-dichloropheny1)-1,1-dimethylurea] in the urothelial mucosa of Wistar rats. Toxicology, v. 312, p. 1-5, . (06/60506-1)
DA ROCHA, MITSCHELI S.; NASCIMENTO, MERIELEN G.; CARDOSO, ANA PAULA F.; DE LIMA, PATRICIA L. A.; ZELANDI, EDNEIA A.; DE CAMARGO, JOAO LAURO V.; DE OLIVEIRA, MARIA LUIZA C. S.. Cytotoxicity and Regenerative Proliferation as the Mode of Action for Diuron-Induced Urothelial Carcinogenesis in the Rat. TOXICOLOGICAL SCIENCES, v. 113, n. 1, p. 37-44, . (06/60506-1)
DE CAMARGO, MARCELA RODRIGUES; TERUYA AKAMINE, PEDRO VINICIUS; VENTURINI, JAMES; DE ARRUDA, MARIA SUELI P.; DA SILVA FRANCHI, CARLA ADRIENE. Pesticide dichorvos induces early solid Ehrlich tumoral development associated with a non-protective pro-inflammatory response. Environmental Science and Pollution Research, v. 25, n. 8, SI, p. 7681-7687, . (06/60506-1)
IHLASEH-CATALANO, SHADIA M.; BAILEY, KATHRYN A.; CARDOSO, ANA PAULA F.; REN, HONGZU; FRY, REBECCA C.; DE CAMARGO, JOAO LAURO V.; WOLF, DOUGLAS C.. Dose and temporal effects on gene expression profiles of urothelial cells from rats exposed to diuron. Toxicology, v. 325, p. 21-30, . (06/60506-1, 09/02754-7)
DA ROCHA, MITSCHELI SANCHES; ARNOLD, LORA L.; COTRIM SARTOR DE OLIVEIRA, MARIA LUIZA; IHLASEH CATALANO, SHADIA M.; FERRAGUT CARDOSO, ANA PAULA; PONTES, MERIELEN G. N.; FERRUCIO, BIANCA; DODMANE, PUTTAPPA R.; COHEN, SAMUEL M.; DE CAMARGO, JOAO LAURO V.. Diuron-induced rat urinary bladder carcinogenesis: Mode of action and human relevance evaluations using the International Programme on Chemical Safety framework. CRITICAL REVIEWS IN TOXICOLOGY, v. 44, n. 5, p. 393-406, . (06/60506-1, 09/02754-7)
IHLASEH, SHADIA M.; BAILEY, KATHRYN A.; HESTER, SUSAN D.; JONES, CARLTON; REN, HONGZU; CARDOSO, ANA PAULA F.; OLIVEIRA, MARIA LUIZA C. S.; WOLF, DOUGLAS C.; DE CAMARGO, JOAO LAURO V.. Transcriptional Profile of Diuron-Induced Toxicity on the Urinary Bladder of Male Wistar Rats to Inform Mode of Action. TOXICOLOGICAL SCIENCES, v. 122, n. 2, p. 330-338, . (06/60506-1, 09/02754-7)
DE CAMARGO, MARCELA RODRIGUES; BARBISAN, LUIS FERNANDO; MARTINEZ, MEIRE FRANCA; DA SILVA FRANCHI, CARLA ADRIENE; VIANA DE CAMARGO, JOAO LAURO; TOZZI SPINARDI-BARBISAN, ANA LUCIA. Macrophage activity and histopathology of the lymphohematopoietic organs in male Wistar rats orally exposed to single or mixed pesticides. JOURNAL OF ENVIRONMENTAL SCIENCE AND HEALTH PART B-PESTICIDES FOOD CONTAMIN, v. 48, n. 7, p. 607-613, . (06/60506-1)

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