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Microtubule assembly inhibition by porphyrins and related compounds.

Authors
Boekelheide-K; Eveleth-J; Tatum-AH; Winkelman-JW
Source
Photochem Photobiol 1987 Nov; 46(5):657-661
NIOSHTIC No.
20036914
Abstract
Administration of meso-tetra(4-sulfonatophenyI)porphine (TPPS4) to rats resulted in cyto-skeletal abnormalities with loss of microtubules in unmyelinated peripheral nerve axons (Winkelman and Collins, 1987). That in vivo toxic effect prompted the present in vitro study of microtubule assembly inhibition by porphyrins and related compounds. Several approaches were used to measure microtubule assembly inhibition including: (1) determination of the final optical density at 350 nm, (2) analysis of supernatant unassembled tubulin by direct measurement and by colchicine binding, and (3) ultrastructural examination for the presence of typical microtubule profiles. Of the 11 compounds studied, TPPS4, two less sulfonated TPPS congeners and me.so-tetra(N'-methyl-4-pyridyl)porphine caused profound microtubule assembly inhibition. Afoo-tetra(4-carboxyphenyl)porphinc produced an intermediate level of microtubule assembly inhibition. The remaining compounds, including hemato-porphyrin D (HpD), had little or no effect upon microtubule assembly. In phytohemagglutinin stimulated lymphocytes, nonphotoactivated TPPS4 produced metaphase arrest to the same extent as colcemid. Thus, the specific interaction of TPPS4 with tubulin produces microtubule assembly inhibition in vitro and metaphase arrest in cell culture. Tubulin binding could explain the intracellular concentration of TPPS4 and TPPS-like compounds, and differences in the biological behavior of these from other porphyrins.
Keywords
Biochemical-analysis; Cell-cultures; Cell-growth; Cell-metabolism; Cellular-reactions; Cellular-structures; In-vivo-studies; Laboratory-animals; Lymphatic-system; Myeloid-tissue; Nerves; Nervous-system-disorders; Neurological-system; Neurophysiological-effects; Neurotoxicity; Photochemical-reactions; Toxic-effects
Contact
James W. Winkelman, Department of Pathology, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA
CODEN
PHCBAP
Publication Date
19871101
Document Type
Journal Article
Funding Amount
357615
Funding Type
Grant
Fiscal Year
1988
NTIS Accession No.
NTIS Price
Identifying No.
Grant-Number-R01-OH-002191
Issue of Publication
5
ISSN
0031-8655
Priority Area
Reproductive-system-disorders
Source Name
Photochemistry and Photobiology
State
RI; NY; MA
Performing Organization
Brown University, Providence, Rhode Island
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