Cytotoxic effects of m-[131I]- and m-[125I]iodobenzylguanidine on the human neuroblastoma cell lines SK-N-SH and SK-N-LO. 1988

G Bruchelt, and R Girgert, and J Buck, and H Wolburg, and D Niethammer, and J Treuner
Department of Pediatrics, University of Tuebingen, West Germany.

As we have reported recently, the human neuroblastoma cell line SK-N-SH is able to take up and store m-iodobenzylguanidine (mIBG). This is in contrast to several other neuroblastoma cell lines, among which are SK-N-LO cells. Both cell lines were used in cell killing experiments with unlabeled and radioactive-labeled mIBG. Using 1-200 microCi m-[131I]IBG (1 h incubation time), only SK-N-SH cells could to a large extent be destroyed in a dose-dependent manner. This effect is completely caused by the radioactive labeling of the molecule, because unlabeled mIBG proved not to be toxic in the concentration range used in experiments with radiolabeled mIBG (30 nM-3 microM). The killing effect was strongly reduced when m-[131I]IBG with low specific activity (0.2-0.3 mCi/mg) was used instead of 20-30 mCi/mg. Similar effects in both cell lines were obtained using m-[131I]-and m-[125I]IBG. SK-N-SH cells that survived a first treatment with m-[131I]IBG were less sensitive to a second treatment. SK-N-LO cells were more sensitive against m-[131I]- and m-[125I]IBG than SK-N-SH cells if both cell lines are exposed to these radioactive compounds over a long period of time (24 h). The reason that only SK-N-SH cells could be destroyed in short-term incubation experiments is that mIBG is stored for approximately 7 days in these cells only. SK-N-LO cells could only be destroyed to a significant degree if m-[131I]IBG was permanently present in the test system. Bone marrow stem cells (CFU-c) also proved to be sensitive against m-[131I]IBG, although the effects were less pronounced than on SK-N-SH cells.

UI MeSH Term Description Entries
D007457 Iodine Radioisotopes Unstable isotopes of iodine that decay or disintegrate emitting radiation. I atoms with atomic weights 117-139, except I 127, are radioactive iodine isotopes. Radioisotopes, Iodine
D007462 Iodobenzenes Any derivative of BENZENE that contains IODINE.
D009447 Neuroblastoma A common neoplasm of early childhood arising from neural crest cells in the sympathetic nervous system, and characterized by diverse clinical behavior, ranging from spontaneous remission to rapid metastatic progression and death. This tumor is the most common intraabdominal malignancy of childhood, but it may also arise from thorax, neck, or rarely occur in the central nervous system. Histologic features include uniform round cells with hyperchromatic nuclei arranged in nests and separated by fibrovascular septa. Neuroblastomas may be associated with the opsoclonus-myoclonus syndrome. (From DeVita et al., Cancer: Principles and Practice of Oncology, 5th ed, pp2099-2101; Curr Opin Oncol 1998 Jan;10(1):43-51) Neuroblastomas
D009638 Norepinephrine Precursor of epinephrine that is secreted by the ADRENAL MEDULLA and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers, and of the diffuse projection system in the brain that arises from the LOCUS CERULEUS. It is also found in plants and is used pharmacologically as a sympathomimetic. Levarterenol,Levonorepinephrine,Noradrenaline,Arterenol,Levonor,Levophed,Levophed Bitartrate,Noradrenaline Bitartrate,Noradrénaline tartrate renaudin,Norepinephrin d-Tartrate (1:1),Norepinephrine Bitartrate,Norepinephrine Hydrochloride,Norepinephrine Hydrochloride, (+)-Isomer,Norepinephrine Hydrochloride, (+,-)-Isomer,Norepinephrine d-Tartrate (1:1),Norepinephrine l-Tartrate (1:1),Norepinephrine l-Tartrate (1:1), (+,-)-Isomer,Norepinephrine l-Tartrate (1:1), Monohydrate,Norepinephrine l-Tartrate (1:1), Monohydrate, (+)-Isomer,Norepinephrine l-Tartrate (1:2),Norepinephrine l-Tartrate, (+)-Isomer,Norepinephrine, (+)-Isomer,Norepinephrine, (+,-)-Isomer
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
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
D004298 Dopamine One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action. Hydroxytyramine,3,4-Dihydroxyphenethylamine,4-(2-Aminoethyl)-1,2-benzenediol,Dopamine Hydrochloride,Intropin,3,4 Dihydroxyphenethylamine,Hydrochloride, Dopamine
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
D019797 3-Iodobenzylguanidine A guanidine analog with specific affinity for tissues of the sympathetic nervous system and related tumors. The radiolabeled forms are used as antineoplastic agents and radioactive imaging agents. (Merck Index, 12th ed) MIBG serves as a neuron-blocking agent which has a strong affinity for, and retention in, the adrenal medulla and also inhibits ADP-ribosyltransferase. (3-Iodo-(131I)benzyl)guanidine,Iobenguane,MIBG,3-Iodobenzylguanidine, 123I Labeled,3-Iodobenzylguanidine, 125I Labeled,Iobenguane (131I),m-Iodobenzylguanidine,meta-Iodobenzylguanidine,123I Labeled 3-Iodobenzylguanidine,125I Labeled 3-Iodobenzylguanidine,3 Iodobenzylguanidine,3 Iodobenzylguanidine, 123I Labeled,3 Iodobenzylguanidine, 125I Labeled,m Iodobenzylguanidine,meta Iodobenzylguanidine

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