Identification and characterization of cysteinyl-leukotriene formation in tissue slices from human intracranial tumors: evidence for their biosynthesis under in vivo conditions.
In previous studies, it had been shown that human gray and white matter tissue slices have the capacity to synthesize large amounts of cysteinyl-leukotrienes (cysteinyl-LT) in vitro. This study was initiated to investigate cysteinyl-LT formation by tissue slices from intracranial tumors in comparison with cyclooxygenase products such as prostaglandin (PG) F2 alpha and thromboxane (TX) B2. Tissue slices from meningiomas and astrocytomas were found to release large amounts of cysteinyl-LT spontaneously and even higher amounts after ionophore A 23187 stimulation, which could not be accounted for by blood possibly remaining in the tissue slices. Cysteinyl-LT were identified by their immunoreactive characteristics, their biological activity in the guinea pig ileum bioassay, and their retention time on reversed-phase HPLC. With increasing malignancy, astrocytomas were shown to have an increasing biosynthetic capacity for cysteinyl-LT and TXB2 in vitro. In comparison with meningioma patients, malignant astrocytoma patients had an enhanced urinary excretion of LTE4, the major urinary metabolite of cysteinyl-LT in humans, which dropped in level within 7 days after operation by 79%. A correlation exists between the in vivo cysteinyl-LT production in patients with malignant astrocytomas and that observed under basal conditions in the tissue slices in vitro. The results provide evidence that in malignant astrocytoma patients, the tumor tissue produces large amounts of cysteinyl-LT, which may be detected in the patients' urine.
Simmet
T
T
Department of Pharmacology, Ruhr-University, Bochum, F.R.G.
Luck
W
W
Winking
M
M
Delank
W K
WK
Peskar
B A
BA
D001254:Astrocytoma / Q000097:blood / Q000378:metabolism*; D001681:Biological Assay; D001932:Brain Neoplasms / Q000097:blood / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D003545:Cysteine / Q000096:biosynthesis; D015777:Eicosanoids / Q000096:biosynthesis; D006801:Humans; D066298:In Vitro Techniques; D015289:Leukotrienes / Q000096:biosynthesis*; D008577:Meningeal Neoplasms / Q000097:blood / Q000378:metabolism*; D008579:Meningioma / Q000097:blood / Q000378:metabolism*; D013189:SRS-A / Q000096:biosynthesis / Q000097:blood / Q000652:urine
D015777:Eicosanoids; D015289:Leukotrienes; D013189:SRS-A; D003545:Cysteine