Nucleoside transport in normal and neoplastic cells

Belt, Judith A.; Marina, Neyssa; Phelps, Doris A.; Crawford, Charles R.

doi:10.1016/0065-2571(93)90021-5

Cited by 156 publications

(111 citation statements)

References 38 publications

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“…Dipyridamole (DP), because of its known interaction with nucleoside transport (Plagemann et al, 1988;Belt et al, 1993), has been most extensively studied as an augmentor of antimetabolite cytotoxicity (Schmoll et al, 1990;Goel and Howell, 1991 and references therein). Nevertheless, several studies have demonstrated the potentiation of other agents by DP.…”

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confidence: 99%

Dipyridamole increases VP16 growth inhibition, accumulation and retention in parental and multidrug-resistant CHO cells

Turner

Curtin²

1996

Br J Cancer

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Summary Dipyridamole (DP) has been shown to reverse multidrug resistance (MDR) via interactions with Pglycoprotein (P-gp). The effect of DP on VP16 growth inhibition was investigated in parental (CHO-KI) and MDR (CHO-AdrD Chinese hamster ovary cells. CHO-Adrr cells were 18-fold resistant to VP16 and intracellular accumulation was 28% less than in CHO-Ki cells. DP reduced the resistance of CHO-Adrr to VP16 by a factor of 2-3 and caused a similar potentiation of VP16 growth inhibition in the parental cells. A time-dependent increase in intracellular VP16 accumulation, which was similar in both cell lines, was caused by DP. The intracellular retention of VP16 was increased 2-to 3-fold by DP in both cell lines. The magnitude of the effect of DP on all three parameters measured was similar (2-to 4-fold), suggesting that the increased growth inhibition was related to increased intracellular exposure to VP16 owing to the inhibition of the efflux of VP16 by DP. However, since the effect of DP was similar in both parental and P-gp-overexpressing cells it is unlikely that the potentiation of VP16 by DP is mediated via an interaction with P-gp.

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confidence: 99%

Dipyridamole increases VP16 growth inhibition, accumulation and retention in parental and multidrug-resistant CHO cells

Turner

Curtin²

1996

Br J Cancer

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“…16 Nucleoside uptake into most cell types is mediated by equilibrative transport systems that take up their substrates down a concentration gradient, which is generated by active intracellular metabolism of these compounds. [17][18][19] Facilitative nucleoside transport systems correspond to at least two independent kinetic components, which differ in their sensitivity to the nucleoside analogue NBTI. [17][18][19] NBTI-sensitive and NBTI-insensitive carrier-related cDNAs have recently been cloned from human and rat tissues.…”

mentioning

confidence: 99%

“…[17][18][19] Facilitative nucleoside transport systems correspond to at least two independent kinetic components, which differ in their sensitivity to the nucleoside analogue NBTI. [17][18][19] NBTI-sensitive and NBTI-insensitive carrier-related cDNAs have recently been cloned from human and rat tissues. [20][21][22][23] In contrast, highly specialized cell types, like those from absorptive epithelia, show concentrative agencies that are Na ϩ -dependent but differ in their substrate specificity.…”

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confidence: 99%

Differential expression and regulation of nucleoside transport systems in rat liver parenchymal and hepatoma cells

et al. 1998

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Primary cultures of rat-liver parenchymal cells show carrier-mediated nucleoside uptake by a mechanism that mainly involves concentrative, Na ؉ -dependent transport activity. In contrast, the hepatoma cell line FAO shows high nucleoside transport activity, although it is mostly accounted for by Na ؉ -independent transport processes. This is associated with a low amount of sodium purine nucleoside transporter (SPNT) mRNA. SPNT encodes a purinepreferring transporter expressed in liver parenchymal cells. To analyze whether SPNT expression is modulated during cell proliferation, SPNT mRNA levels were determined in the early phase of liver growth after partial hepatectomy and in synchronized FAO cells that had been induced to proliferate. SPNT mRNA amounts increased as early as 2 hours after partial hepatectomy. FAO cells induced to proliferate after serum refeeding show an increase in SPNT mRNA levels, which is followed by an increase in Na ؉ -dependent nucleoside uptake and occurs before the peak of 3 H-thymidine incorporation into DNA. FAO cells also express significant equilibrative nucleoside transport activity, which may be accounted for by the expression of the nitrobenzylthioinosine (NBTI)-sensitive and -insensitive isoforms, rat equilibrative nucleoside transporter 1 (rENT1) and rENT2, respectively. Interestingly, rENT2 mRNA levels follow a similar pattern to that described for SPNT when FAO cells are induced to proliferate, whereas rENT1 appears to be constitutively expressed. Liver parenchymal cells show low and negligible mRNA levels for rENT1 and rENT2 transporters, respectively, although most of the equilibrative transport activity found in hepatocytes is NBTI-resistant. It is concluded that: 1) SPNT expression is regulated both in vivo and in vitro in a way that appears to be dependent on cell cycle progression; 2) SPNT expression may be a feature of differentiated hepatocytes; and 3) equilibrative transporters are differentially regulated, rENT2 expression being cell cycle-dependent. This is consistent with its putative role as a growth factor-induced delayed early response gene. (HEPATOLOGY 1998;28:1504-1511.)Nucleosides and nucleoside analogues have a wide range of potent physiological and pharmacological properties. Purines, essentially adenosine, play a multifactorial role in liver physiology by modulating key metabolic pathways of the hepatocyte 1-5 and influencing, among other functions, hepatic arterial pressure-flow autoregulation, 6 vasodilation, 7 and superoxide anion generation. 8

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“…23,35,36 TP-treated serum is needed because early progenitor cells can resist antifolates such as TMTX by utilizing nucleoside salvage pathways to bypass the de novo synthesis block. [40][41][42][43] The inclusion of TMTX in the culture medium during the 2-week DC differentiation and expansion significantly increased the percentage of marked DC (Figure 4, Tables 1 and 2). Selection with TMTX was found to be equally effective for both lentivirus-and retrovirus-transduced cells, indicating the potential usefulness of this system to produce highly enriched populations of DC expressing transgenes.…”

Section: Discussionmentioning

confidence: 99%

Pre-clinical evaluation of an in vitro selection protocol for the enrichment of transduced CD34+ cell-derived human dendritic cells

et al. 2001

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The efficient genetic modification of CD34 + cell-derived dendritic cells (DC) will provide a significant advancement towards the development of immunotherapy protocols for cancer, autoimmune disorders and infectious diseases. Recent reports have described the transduction of CD34 + cells via retrovirus-and lentivirus-based gene transfer vectors and subsequent differentiation into functional DC. Since there is significant apprehension regarding the clinical uses of HIV-based vectors, in this report, we compare a murine leukemia virus (MLV)-and a human immunodeficiency virus (HIV)-based bicistronic vector for gene transfer into human

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Nucleoside transport in normal and neoplastic cells

Cited by 156 publications

References 38 publications

Dipyridamole increases VP16 growth inhibition, accumulation and retention in parental and multidrug-resistant CHO cells

Dipyridamole increases VP16 growth inhibition, accumulation and retention in parental and multidrug-resistant CHO cells

Differential expression and regulation of nucleoside transport systems in rat liver parenchymal and hepatoma cells

Pre-clinical evaluation of an in vitro selection protocol for the enrichment of transduced CD34+ cell-derived human dendritic cells

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