Differential effect of alpha-difluoromethylornithine on the in vivo uptake of 14C-labeled polyamines and methylglyoxal bis(guanylhydrazone) by a rat prostate-derived tumor

Journal Article · Thu Mar 01 04:00:00 EST 1984 · Cancer Res.; (United States)

OSTI ID:6351984

Heston, W D; Kadmon, D; Covey, D F; Fair, W R

The uptake of exogenously administered radiolabeled polyamines by a rat prostate-derived tumor line, the Dunning R3327 MAT-Lu, and various normal tissues was studied. Pretreatment of tumor cells in vitro with alpha-difluoromethylornithine (DFMO), a polyamine synthesis inhibitor, resulted in a markedly enhanced uptake of both (/sup 14/C)putrescine and (14 C)spermidine. The in vitro uptake of (/sup 14/C)putrescine by these cells was effectively inhibited by unlabeled spermine, spermidine, 1,8-diaminooctane, 1,7-diaminoheptane, 1,6-diaminohexane, 1,5-diaminopentane, 1,4-diaminopentane, and 1,4-diaminobutane, but less effectively by 1,4-diamino-2,3-butene and 1,4-diamino-2,3-butyne. The diamines, 1,3-diaminopropane and 1,2-diaminoethane, were ineffective in inhibiting (/sup 14/C)putrescine uptake in vitro into the R3327 MAT-Lu cell line. When tumor-bearing animals were pretreated with DFMO or with DFMO and 5-alpha-dihydrotestosterone propionate, the tumor and prostate uptake of (/sup 14/C)putrescine and (/sup 14/C)-cadaverine was enhanced but not substantially increased in other tissues. In contrast to the in vitro results, spermidine and spermine were not enhanced substantially by DFMO pretreatment into any tissue, and their uptake into the tumor actually decreased. Ethylenediamine, which does not utilize the polyamine transport system, did not have its uptake increased into any tissue following DFMO pretreatment. The chemotherapeutic agent, methylglyoxal bis(guanylhydrazone), which utilizes the polyamine transport system for uptake into cells, exhibited uptake behavior different from that of the polyamines.

• Research Organization: Washington Univ., St. Louis, MO
• OSTI ID: 6351984
• Journal Information: Cancer Res.; (United States), Journal Name: Cancer Res.; (United States) Vol. 44:3; ISSN CNREA
• Country of Publication: United States
• Language: English

Related Subjects

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560306* -- Chemicals Metabolism & Toxicology-- Man-- (-1987)
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
AMINES
ANIMALS
ANTINEOPLASTIC DRUGS
BIOLOGICAL EFFECTS
BODY
CADAVERINE
CARBON 14 COMPOUNDS
DISEASES
DRUGS
GLANDS
IN VIVO
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
MALE GENITALS
MAMMALS
NEOPLASMS
ORGANIC COMPOUNDS
ORGANS
PROSTATE
PUTRESCINE
RATS
RODENTS
SPERMIDINE
TRACER TECHNIQUES
UPTAKE
VERTEBRATES