Transgenic mice expressing the Sh ble bleomycin resistance gene are protected against bleomycin-induced pulmonary fibrosis
| Autor: | Weinbach, J., Anne Camus, Barra, J., Dumont, P., Julian, M., Cros, S., Babinet, C., Tiraby, G. |
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| Přispěvatelé: | Regenerative Medicine and Skeleton research lab (RMeS), Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM), Bases Génétiques, Moléculaires et Cellulaires du Développement (BGMCD), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Agence Universitaire de la Francophonie (AUF), Unité de biologie cellulaire et moléculaire, Institut National de la Recherche Agronomique (INRA), InvivoGen Europe |
| Jazyk: | angličtina |
| Rok vydání: | 1996 |
| Předmět: |
Antimetabolites
Antineoplastic MESH: Mice Transgenic Pulmonary Fibrosis [SDV]Life Sciences [q-bio] Drug Resistance Mice Transgenic [SDV.CAN]Life Sciences [q-bio]/Cancer [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC] Transfection Bleomycin Mice Bacterial Proteins Species Specificity Acetyltransferases MESH: Mice Inbred C57BL [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO] Animals MESH: Species Specificity MESH: Animals MESH: Antibiotics Antineoplastic MESH: Bacterial Proteins MESH: Mice MESH: Antimetabolites Antineoplastic Antibiotics Antineoplastic MESH: Pulmonary Fibrosis MESH: Transfection MESH: Acetyltransferases [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry Molecular Biology/Molecular biology Survival Analysis MESH: Bleomycin Mice Inbred C57BL Hydroxyproline [SDV.GEN.GA]Life Sciences [q-bio]/Genetics/Animal genetics MESH: Hydroxyproline MESH: Survival Analysis MESH: Drug Resistance Female MESH: Female |
| Zdroj: | Cancer Research Cancer Research, American Association for Cancer Research, 1996, 56 (24), pp.5659-65 HAL |
| ISSN: | 0008-5472 1538-7445 |
| Popis: | International audience; Despite the high efficiency of bleomycin (BLM) as a chemotherapeutic agent against various carcinomas, the potentially lethal and chronic fibrotic response of the lung is a major dose-limiting side effect. Here, we explore the possibility of a direct inhibition of lung tissue injury by in vivo expression of the actinomycetes BLM resistance protein Sh ble. Transgenic mice expressing the Sh ble gene under the control of a composite viral promoter were produced after introduction of the transgene into D3 ES cells. The protein was detected at high level in lungs, spleen, and kidney. We then assessed its ability to modulate the BLM-induced fibrotic response in the transgenic mice in comparison with C57BL/6 and 129/Sv parental mice. Cumulative doses of 300, 400, or 500 mg/kg BLM were administered either by i.p. or s.c. repeated injections in the different strains. Transgenic mice were shown to be clearly less sensitive to BLM toxicity, as assessed by lung histology. The pulmonary hydroxyproline content in the treated transgenic mice was close to its baseline level, whereas it was up to 50% higher than the control level in C57BL/6 and 129/Sv parental mice. These observations are consistent with the hypothesis that a resistance gene specifically expressed in lungs may prevent the BLM-induced inflammation. |
| Databáze: | OpenAIRE |
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