title: Absence of methylthioadenosine phosphorylase in human gliomas.
abstract: All normal mammalian tissues contain methylthioadenosine phosphorylase, which plays a role in the recycling of purines and methionine consumed during polyamine synthesis. A complete deficiency of methylthioadenosine phosphorylase has been reported in some human leukemias and lymphomas and in a few solid tumors. The exact incidence of the enzyme deficiency among fresh human tumor specimens has been difficult to establish because the measurement of enzyme catalytic activity is laborious and requires carefully preserved specimens. We have generated two antibodies against methylthioadenosine phosphorylase and have used them to develop a simple immunoblot assay for the enzyme. Specifically, studies showed that all cells with catalytically active methylthioadenosine phosphorylase had a 32-kDa band that reacted with the anti-enzyme antibodies. In a reciprocal manner, all malignant cell lines that were naturally deficient in methylthioadenosine phosphorylase activity lacked detectable immunoreactive enzyme protein. The immunoassay was used to analyze human gliomas. Seventy-five % (9 of 12) of the gliomas were completely methylthioadenosine phosphorylase deficient. This common metabolic difference between most gliomas and all normal cells is a potential target for tumor-specific chemotherapy.
authors.affiliation: Department of Medicine, University of California, San Diego, La Jolla 92093-0945.
authors.forename: T
authors.initials: T
authors.lastname: Nobori
authors.forename: J G
authors.initials: JG
authors.lastname: Karras
authors.forename: F
authors.initials: F
authors.lastname: Della Ragione
authors.forename: T A
authors.initials: TA
authors.lastname: Waltz
authors.forename: P P
authors.initials: PP
authors.lastname: Chen
authors.forename: D A
authors.initials: DA
authors.lastname: Carson
mesh_terms: D000818:Animals; D001706:Biopsy; D001932:Brain Neoplasms / Q000201:enzymology* / Q000473:pathology / Q000601:surgery; D002460:Cell Line; D004797:Enzyme-Linked Immunosorbent Assay; D005910:Glioma / Q000201:enzymology* / Q000473:pathology / Q000601:surgery; D006801:Humans; D015151:Immunoblotting; D011683:Purine-Nucleoside Phosphorylase / Q000032:analysis* / Q000172:deficiency
chemical_list: D011683:Purine-Nucleoside Phosphorylase; C021784:5'-methylthioadenosine phosphorylase