Journal article
Organ-specific differences in the metabolism of N6-(Δ 2-isopentenyl)-adenosine
Biochemical pharmacology, Vol.25(18), pp.2059-2065
1976
DOI: 10.1016/0006-2952(76)90430-5
PMID: 985544
Abstract
N
6-(Δ
2-isopentenyl-adenosine (IPAR) is a modified ribonucleoside with antitumor activity limited at least in part by severe hepatotoxic effects observed in rodents and patients. Four hr after i.v. administration of IPAR[8
14C] to rats, the drug is phosphorylated to the 5′-mono, di-, and triphosphates, and incorporated into RNA but not into DNA and protein of liver and small intestine. In contrast, in spleen and thymus, the drug is phosphorylated to the 5′-monophosphate (5′-IPAMP) only with no detectable incorporation of the drug into DNA, RNA or protein. The initial phosphorylation of IPAR to 5′-IPAMP in liver at 30 min is accompanied by a 70 per cent reduction in the ATP pool and an accumulation of 2.0 μmoles IPAMP/g. In thymus, the drug reduces the size of pyrimidine ribonucleotide pools, resulting in a 2- to 5-fold increase in the specific activity of [
14C]pyrimidine ribonucleotides. These effects may contribute to the understanding of the biochemical basis for selective cytotoxicity of
N
6-isopentenyl adenosine.
Details
- Title: Subtitle
- Organ-specific differences in the metabolism of N6-(Δ 2-isopentenyl)-adenosine
- Creators
- Youcef M. Rustum - Roswell Park Cancer InstituteHerbert S. Schwartz - Roswell Park Cancer Institute
- Resource Type
- Journal article
- Publication Details
- Biochemical pharmacology, Vol.25(18), pp.2059-2065
- Publisher
- Elsevier Inc
- DOI
- 10.1016/0006-2952(76)90430-5
- PMID
- 985544
- ISSN
- 0006-2952
- eISSN
- 1873-2968
- Language
- English
- Date published
- 1976
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984359691702771
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