This is Part 2 of a presentation on Genetic Toxicology that was given by Dr. David Kirkland to scientific staff at Health Canada in Nov. 2010. Part 1 is availabile here in ppt and as a webinar at the LinkedIn DABT CE group link
This is Part 1 of a presentation on Genetic Toxicology that was given by Dr. David Kirkland to scientific staff at Health Canada in Sept. 2010. Part 2 is availabile in ppt
This is Part 1 of a presentation on Genetic Toxicology that was given by Dr. David Kirkland to scientific staff at Health Canada in Sept. 2010. Part 2 is availabile in ppt
Fundamentals Of Genetic Toxicology In The Pharmaceutical Industry Sept 2010TigerTox
Historical and current perspectives on genetic toxicology, with commentary and slides on assay predictivity and shortcomings, regulatory guidance, and high-throughput screens to enhance preclinical drug safety.
This is a lecture by Dr. Jerry McLaughlin about his research into extracts of pawpaw plants, annonaceous acetogenins, in vitro, in vivo, mechanism of action, and toxicity in mice.
This presentation gives the brief idea of the various guidelines carried out to study the genetic damage to cells when there is a discover of new active molecule.
V79C cells were derived from V79 cell line by through chronic oxidative stress that was found to be radio-resistant. These cells had demonstrated transformation–like stable changes and could be used as model system to study oxidant induced carcinogenesis. Our objective was to understand mechanism of radiation-resistance in these cells. Apoptotic cell death was inhibited in these cells as visualized microscopically by Hoechst staining and nucleosomal ladder formation in agarose gel. Release of cytochrome c in cytoplasm and Apoptosis Inducing Factor in the mitochondrial and nuclear fraction of cells were determined by Western blotting. The caspase 9 and caspase 3 activities in these cells were estimated from fluorimetric assays. These results revealed that the radiation resistance was due to inhibition of caspase-dependent apoptotic death pathways although Apoptosis Inducing Factor mediated pathway remained unaffected. These findings may aid in understanding the mechanism of radiation resistance in tumors arising from oxidative stress.
Fundamentals Of Genetic Toxicology In The Pharmaceutical Industry Sept 2010TigerTox
Historical and current perspectives on genetic toxicology, with commentary and slides on assay predictivity and shortcomings, regulatory guidance, and high-throughput screens to enhance preclinical drug safety.
This is a lecture by Dr. Jerry McLaughlin about his research into extracts of pawpaw plants, annonaceous acetogenins, in vitro, in vivo, mechanism of action, and toxicity in mice.
This presentation gives the brief idea of the various guidelines carried out to study the genetic damage to cells when there is a discover of new active molecule.
V79C cells were derived from V79 cell line by through chronic oxidative stress that was found to be radio-resistant. These cells had demonstrated transformation–like stable changes and could be used as model system to study oxidant induced carcinogenesis. Our objective was to understand mechanism of radiation-resistance in these cells. Apoptotic cell death was inhibited in these cells as visualized microscopically by Hoechst staining and nucleosomal ladder formation in agarose gel. Release of cytochrome c in cytoplasm and Apoptosis Inducing Factor in the mitochondrial and nuclear fraction of cells were determined by Western blotting. The caspase 9 and caspase 3 activities in these cells were estimated from fluorimetric assays. These results revealed that the radiation resistance was due to inhibition of caspase-dependent apoptotic death pathways although Apoptosis Inducing Factor mediated pathway remained unaffected. These findings may aid in understanding the mechanism of radiation resistance in tumors arising from oxidative stress.
La disponibilidad de un sistema de multiplicación del virus de la hepatitis C (VHC) infeccioso en cultivos celulares está permitiendo investigar nuevos factores de respuesta a tratamientos antivíricos en condiciones controladas. Se presentará evidencia de que el fitness vírico puede ser un factor de multiresistencia a inhibidores y quese pueden obtener eficientes reducciones de carga viral empleando diseños secuenciales de administración de inhibidores que incluyan ribavirina. Se discutirán posibilidades de aplicación clínica.
3. DMEM F-10 F-12 RPMI RPMI McCoys Williams Hepes 5A E M of H 2 O 2 produced - + - + - + - + - + - + - + EGCG Sig. clastogenic dose of H 2 O 2
4. % cells with CA (solid line) Relative cell count (%) (dashed line) Incubation time (hr) of EGCG in medium before stopping reaction McCoy’s 5A F-10
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6. Chemical Previous LEC New LEC Allyl isovalerate 2.81 mM in MLA +ve at 0.55 mM in CA (3 hr +S9) Benzofuran 1.27 mM in MLA -ve at in MLA up to 1 mM (64-99% toxicity ). Increased MF at 2 mM but almost 100% toxicity Caffeic acid 1.11 mM in MLA +ve 0.4 mM in MLA (24 hr –S9) and 1 mM in CA (20 hr –S9) Chlorobenzene 1.11 mM in MLA +ve at 0.6 mM in MLA (3 hr +S9) Daminozide 13.75 mM in CA; 11.25 mM in MLA -ve up to 10 mM (CA & MLA) Furan 1.47 mM in CA +ve at 0.8 mM in MLA (3 hr +S9) and at 4 mM in CA (3 hr +S9) Methylolacrylamide 2.94 mM in CA +ve at 2 mM in CA (20 hr –S9) and MLA (24 hr –S9) Toluene 2.44 mM in MLA -ve up to toxic doses (10% RTG) in MLA (not tested in CA) Monuron 6.54 mM in CA -ve in CA up to 4.25 mM which induced >50% toxicity (- and + S9)
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8. % cells with CA Survival measure relative to control Conc. of drug( g/ml) 50% toxicity
31. In vivo micronucleus assay 6-8 h 18-22 h Erythroblasts Immature erythrocytes Mature erythrocytes Bone marrow Peripheral blood Clastogen
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36. Peripheral Blood MN Methodology Inside the Cytometer FITC PI 488nm laser NCE (No Fluorescence) Reticulocyte (Green) MN-Reticulocyte (Green + Red) Platelet (Yellow) Key PE