Cell interactions in abnormal neural tube and neural crest cell development of splotch mice

Early identification of mutant embryos prior to the manifestation of a defect facilitates the study of dysmorphogenesis. The In(l)lRk inversion was used as a cytogenetic marker to distinguish embryonic day 9 (D9) splotch (Sp) and splotch-delayed $(Sp sp{d})$ mouse mutants from heterozygous and wild-type littermates, and cellular aspects of abnormal neurulation and NCC migration were examined before inherent neural tube defects (NTDs) and deficiencies in neural crest cell (NCC) derivatives developed. In vitro analysis of NCC emigration from D9 neural tube explants revealed a delay in the release of NCCs from mutant neural tubes compared to controls, suggesting that the primary effect of the mutation was intrinsic to the neuroepithelium. Immunofluorescent localization of the neural cell adhesion molecule (N-CAM) antibody in situ demonstrated an increased intensity of antibody fluorescence in mutant tissue compared to controls, and further characterization by immunoblot analysis showed an altered embryonic N-CAM profile in both Sp and $Sp sp{d}$ mutants at D9 of gestation. The importance of N-CAMs in mediating cellular organization and communication has been well documented, supporting the idea that an alteration in this adhesion mechanism could result in the types of defects seen in splotch locus mouse mutants

REVISÃO REVIEW A Review of Pesticide Exposure and Cancer Incidence in the Agricultural Health Study Cohort

Revisão sobre a exposição aos pesticidas e a incidência de câncer em estudo de coorte da saúde dos agricultores Resumo Nós revisamos evidências epidemioló-gicas relacionadas à exposição ocupacional a pesticidas e à incidência de câncer no Estudo da Saú-de Agrícola (AHS). Descobertas relacionadas com a vida-dia e / ou intensidade do tempo de vidadia do uso de agrotóxicos são o foco principal desta revisão, porque estas medidas permitem a avaliação do potencial das relações de exposição-resposta. A maioria dos 32 pesticidas examinados não foram fortemente associados à incidência de cân-cer em aplicadores de pesticidas. Um aumento da taxa e padrões de resposta-exposição positivos foram reportados em 12 pesticidas registrados atualmente nos Estados Unidos e Canadá. A classificação de exposição incorreta também é uma preocupação para o AHS e pode limitar a análise dos padrões de resposta-exposição. É necessário um acompanhamento contínuo para clarificar as associações reportadas até hoje. Em particular, é necessária uma avaliação mais profunda dos pesticidas registrados. Palavras-chave Estudo de saúde agrícola, Cân-cer, Pesticidas, Revisão Abstract We reviewed epidemiologic evidence related to occupational pesticide exposures and cancer incidence in the Agricultural Health Study (AHS) cohort. Studies were identified from the AHS publication list available on a Medline/ PubMed database search in March 2009. Findings related to lifetime-days and/or intensityweighted lifetime-days of pesticide use are the primary focus of this review, because these measures allow for the evaluation of potential exposure-response relationships. Most of the 32 pesticides examined were not strongly associated with cancer incidence in pesticide applicators. Increased rate ratios and positive exposure-response patterns were reported for 12 pesticides currently registered in Canada and/or the United States. Exposure misclassification is also a concern in the AHS and may limit the analysis of exposureresponse patterns. Epidemiologic evidence outside the AHS remains limited with respect to most of the observed associations, but animal toxicity data support the biological plausibility of relationships observed six pesticides. Continued follow-up is needed to clarify associations reported to date. In particular, further evaluation of registered pesticides is warranted