Primary cultures of microglial cells for testing toxicity of anticancer drugs. 2004

Mauro Vairano, and Grazia Graziani, and Lucio Tentori, and Giuseppe Tringali, and Pierluigi Navarra, and Cinzia Dello Russo
Institute of Pharmacology, Catholic University Medical School, Largo Francesco Vito 1, Rome 00168, Italy.

Toxicity of anticancer agents on normal neural cells during chemotherapy of primary or secondary brain tumors is a clinical problem of increasing relevance and concern. In this perspective, here we used primary cultures of rat cortical microglia as an in vitro paradigm of normal glia to investigate the neurotoxicity of anticancer agents. The effects of two compounds frequently used for treatment of brain tumors, methotrexate (MTX) and temozolomide (TMZ), were compared to those of a known microglial activator, bacterial lipopolysaccharide (LPS); cell viability and metabolism was assessed by the MTS assay. We found that LPS, in the low-intermediate range of concentrations, strongly activates microglia cells, but a highly significant decrease in viability was observed from 100 ng/ml onward. TMZ has no effect at concentrations of clinical interest, whereas MTX significantly increases cell metabolism at 30 microM, a phenomenon possibly reflecting MTX neurotoxicity observed in patients.

UI MeSH Term Description Entries
D008070 Lipopolysaccharides Lipid-containing polysaccharides which are endotoxins and important group-specific antigens. They are often derived from the cell wall of gram-negative bacteria and induce immunoglobulin secretion. The lipopolysaccharide molecule consists of three parts: LIPID A, core polysaccharide, and O-specific chains (O ANTIGENS). When derived from Escherichia coli, lipopolysaccharides serve as polyclonal B-cell mitogens commonly used in laboratory immunology. (From Dorland, 28th ed) Lipopolysaccharide,Lipoglycans
D008727 Methotrexate An antineoplastic antimetabolite with immunosuppressant properties. It is an inhibitor of TETRAHYDROFOLATE DEHYDROGENASE and prevents the formation of tetrahydrofolate, necessary for synthesis of thymidylate, an essential component of DNA. Amethopterin,Methotrexate Hydrate,Methotrexate Sodium,Methotrexate, (D)-Isomer,Methotrexate, (DL)-Isomer,Methotrexate, Dicesium Salt,Methotrexate, Disodium Salt,Methotrexate, Sodium Salt,Mexate,Dicesium Salt Methotrexate,Hydrate, Methotrexate,Sodium, Methotrexate
D009422 Nervous System Diseases Diseases of the central and peripheral nervous system. This includes disorders of the brain, spinal cord, cranial nerves, peripheral nerves, nerve roots, autonomic nervous system, neuromuscular junction, and muscle. Neurologic Disorders,Nervous System Disorders,Neurological Disorders,Disease, Nervous System,Diseases, Nervous System,Disorder, Nervous System,Disorder, Neurologic,Disorder, Neurological,Disorders, Nervous System,Disorders, Neurologic,Disorders, Neurological,Nervous System Disease,Nervous System Disorder,Neurologic Disorder,Neurological Disorder
D002470 Cell Survival The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. Cell Viability,Cell Viabilities,Survival, Cell,Viabilities, Cell,Viability, Cell
D003606 Dacarbazine An antineoplastic agent. It has significant activity against melanomas. (from Martindale, The Extra Pharmacopoeia, 31st ed, p564) DTIC,5-(3,3-Dimethyl-1-triazeno)imidazole-4-carboxamide,Biocarbazine,DIC,DTIC-Dome,Decarbazine,Deticene,Dimethyl Imidazole Carboxamide,Dimethyl Triazeno Imidazole Carboxamide,ICDT,NSC-45388,Carboxamide, Dimethyl Imidazole,DTIC Dome,DTICDome,Imidazole Carboxamide, Dimethyl,NSC 45388,NSC45388
D004354 Drug Screening Assays, Antitumor Methods of investigating the effectiveness of anticancer cytotoxic drugs and biologic inhibitors. These include in vitro cell-kill models and cytostatic dye exclusion tests as well as in vivo measurement of tumor growth parameters in laboratory animals. Anticancer Drug Sensitivity Tests,Antitumor Drug Screens,Cancer Drug Tests,Drug Screening Tests, Tumor-Specific,Dye Exclusion Assays, Antitumor,Anti-Cancer Drug Screens,Antitumor Drug Screening Assays,Tumor-Specific Drug Screening Tests,Anti Cancer Drug Screens,Anti-Cancer Drug Screen,Antitumor Drug Screen,Cancer Drug Test,Drug Screen, Anti-Cancer,Drug Screen, Antitumor,Drug Screening Tests, Tumor Specific,Drug Screens, Anti-Cancer,Drug Screens, Antitumor,Drug Test, Cancer,Drug Tests, Cancer,Screen, Anti-Cancer Drug,Screen, Antitumor Drug,Screens, Anti-Cancer Drug,Screens, Antitumor Drug,Test, Cancer Drug,Tests, Cancer Drug,Tumor Specific Drug Screening Tests
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000077204 Temozolomide A dacarbazine derivative that is used as an alkylating antineoplastic agent for the treatment of MALIGNANT GLIOMA and MALIGNANT MELANOMA. 8-Carbamoyl-3-methylimidazo(5,1-d)-1,2,3,5-tetrazin-4(3H)-one,CCRG 81045,CCRG-81045,M&B 39831,M&B-39831,Methazolastone,NSC 362856,NSC-362856,TMZ-Bioshuttle,TMZA-HE,Temodal,Temodar,Temozolomide Hexyl Ester,CCRG81045,M&B39831,NSC362856,TMZ Bioshuttle
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000831 Animals, Newborn Refers to animals in the period of time just after birth. Animals, Neonatal,Animal, Neonatal,Animal, Newborn,Neonatal Animal,Neonatal Animals,Newborn Animal,Newborn Animals

Related Publications

Mauro Vairano, and Grazia Graziani, and Lucio Tentori, and Giuseppe Tringali, and Pierluigi Navarra, and Cinzia Dello Russo
July 2002, The Lancet. Oncology,
Mauro Vairano, and Grazia Graziani, and Lucio Tentori, and Giuseppe Tringali, and Pierluigi Navarra, and Cinzia Dello Russo
July 2022, Journal of visualized experiments : JoVE,
Mauro Vairano, and Grazia Graziani, and Lucio Tentori, and Giuseppe Tringali, and Pierluigi Navarra, and Cinzia Dello Russo
January 2008, Journal of toxicology and environmental health. Part A,
Mauro Vairano, and Grazia Graziani, and Lucio Tentori, and Giuseppe Tringali, and Pierluigi Navarra, and Cinzia Dello Russo
May 2003, Revue de l'infirmiere,
Mauro Vairano, and Grazia Graziani, and Lucio Tentori, and Giuseppe Tringali, and Pierluigi Navarra, and Cinzia Dello Russo
May 2003, Revue de l'infirmiere,
Mauro Vairano, and Grazia Graziani, and Lucio Tentori, and Giuseppe Tringali, and Pierluigi Navarra, and Cinzia Dello Russo
May 2003, Revue de l'infirmiere,
Mauro Vairano, and Grazia Graziani, and Lucio Tentori, and Giuseppe Tringali, and Pierluigi Navarra, and Cinzia Dello Russo
August 1990, Science (New York, N.Y.),
Mauro Vairano, and Grazia Graziani, and Lucio Tentori, and Giuseppe Tringali, and Pierluigi Navarra, and Cinzia Dello Russo
December 2021, Nephrologie & therapeutique,
Mauro Vairano, and Grazia Graziani, and Lucio Tentori, and Giuseppe Tringali, and Pierluigi Navarra, and Cinzia Dello Russo
April 2012, Toxicology in vitro : an international journal published in association with BIBRA,
Mauro Vairano, and Grazia Graziani, and Lucio Tentori, and Giuseppe Tringali, and Pierluigi Navarra, and Cinzia Dello Russo
January 1983, Acta pharmacologica et toxicologica,
Copied contents to your clipboard!