Published data have suggested a possible link between the tumor promoting activity and the aneugenic properties of griseofulvin. The present study was conducted to explore this relationship. Griseofulvin was evaluated both for its potential promoting activity in liver carcinogenesis in partially hepatectomized F344 male rats initiated by diethylnitrosamine and for its genotoxic potential in the peripheral blood micronucleus assay. Rats were treated daily with 2,000 mg/kg body weight by oral gavage for 12 weeks in the medium-term carcinogenesis bioassay. GST-P-positive foci (mean number and surface area) and altered cell foci were compared in the liver of rats treated with griseofulvin alone, diethylnitrosamine alone,and griseofulvin in addition to diethylnitrosamine by using immunohistochemical and histopathological evaluation, respectively. This evaluation allowed the conclusion that griseofulvin did not initiate the carcinogenic process but rather had a potential in the liver for tumor promoting activity. Griseofulvin was found to be negative in the rat peripheral blood micronucleus test when given at a daily oral dose of 2,000 mg/kg body weight for at least 3 weeks.
This study investigates the kinetics of bone marrow micronucleated polychromatic erythrocytes and some mechanistic aspects of micronuclei induction using mathematical models. Female mice were administered a single intraperitoneal injection of the purine antagonist 6-mercaptopurine at 50 mg kg(-1). The time course evolution of the drug concentrations in the plasma and the micronucleated polychromatic erythrocyte kinetic rate in bone marrow were observed. Two mathematical models were developed for this study. The first model was built from a simultaneous pharmacokinetic/pharmacodynamic approach, but was invalidated after comparing its predictions to experimental data. The second model was a stochastic model based on some biological hypotheses involved in micronuclei induction. This model predicted a wavy kinetic rate of micronucleated polychromatic erythrocytes that was confirmed by a second data set obtained from a specifically built experimental design. The biological hypotheses were then discussed. It turned out from this work that mathematical modelling could be used as a tool to explore the cellular mechanisms of toxicity of the compound: for instance, the assumptions that 6-mercaptopurine induced micronuclei mainly in cells entering the S phase, and not only during the last cell cycle but during one of the earlier cycles preceding the extrusion of the main nucleus, were confirmed. Moreover, the use of the stochastic model would help to schedule more accurately the bone marrow or blood harvesting times in the in vivo rodent micronucleus test.
Summary
A serological ELISA test for diagnosis of avian salmonellosis infections with Salmonella typhimurium or enteritidis has been established. Plates were coated half with a negative antigen and half with a positive antigen. Both negative and positive antigens were adsorbed with a monovalent agglutinant anti Escherichia coli serum prior to being distributed into wells of the plates. Sera from SPF birds and from SPF birds vaccinated and/or inoculated with numerous viruses or bacteria, or sera from conventional birds bacteriologically free of any salmonellosis were tested and the percentage of false positive reactions was inferior than 1%. In groups of birds naturally infected or experimentally inoculated with Salmonella enteritidis or typhimurium the percentages of positive individuals were ranged from 15 to more than 90% according to the doses and routes of inoculation and the delay between contamination and sampling.
Résumé
Un test sérologique pour le dépistage des salmonelloses aviaires à Salmonella typhimurium ou enteritidis a été mis au point. Les plaques étaient sensibilisées pour moitié avec un antigène négatif et pour moitié avec un antigène positif. Les deux antigènes positif et négatif étaient adsorbés avec un sérum agglutinant monovalent anti Escherichia coli avant d'être distribués dans les cupules. Des sérums d'oiseaux E.O.P.S., vaccinés et/ou inoculés avec différents virus ou bactéries ou non, ou des sérums d'oiseaux conventionnels bactériologiquement indemnes de salmonelles ont été testés. Moins de 1% de réactions positives ont été enregistrées. Parmi des lots d'oiseaux infectés naturellement ou expérimentalement inoculés avec Salmonella typhimurium ou enteritidis, les pourcentages d'individus positifs étaient compris entre 15 et plus de 90% selon les voies et doses d'inoculation et le délai entre la contamination et le prélèvement.
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