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Biomedical subjects

R N Turner

Publications and source records attributed to R N Turner.

7 recordsLinked to original sources
PubMed1997

Selective potentiation of lometrexol growth inhibition by dipyridamole through cell-specific inhibition of hypoxanthine salvage.

The novel antifolate lometrexol (5,10-dideazatetrahydrofolate) inhibits de novo purine biosynthesis, and co-incubation with hypoxanthine abolishes its cytotoxicity. The prevention of hypoxanthine rescue from an antipurine antifolate by the nucleoside transport inhibitor dipyridamole was investigated for the first time in nine human and rodent cell lines from seven different tissues of origin. In A549, HeLa and CHO cells, dipyridamole prevented hypoxanthine rescue and so growth was inhibited by the combination of lometrexol, dipyridamole and hypoxanthine, but in HT29, HCT116, KK47, MDA231, CCRF CEM and L1210 cells dipyridamole had no effect and the combination did not inhibit growth. Dipyridamole inhibited hypoxanthine uptake in A549 but not in CCRF CEM cells. Dipyridamole prevented the hypoxanthine-induced repletion of dGTP pools, depleted by lometrexol, in A549 but not in CCRF CEM cells. Thus, the selective growth-inhibitory effect of the combination of lometrexol, dipyridamole and hypoxanthine is apparently due to the dipyridamole sensitivity (ds) or insensitivity (di) of hypoxanthine transport. Both the human and murine leukaemic cells are of the di phenotype. If this reflects the transport phenotype of normal bone marrow it would suggest that the combination of lometrexol, dipyridamole and hypoxanthine might be selectively toxic to certain tumour types and have reduced toxicity to the bone marrow.

Antimetabolites, Antineoplastic↗
PubMed1996

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

Dipyridamole (DP) has been shown to reverse multidrug resistance (MDR) via interactions with P-glycoprotein (P-gp). The effect of DP on VP16 growth inhibition was investigated in parental (CHO-K1) and MDR (CHO-Adr(r)) Chinese hamster ovary cells. CHO-Adr(r) cells were 18-fold resistant to VP16 and intracellular accumulation was 28% less than in CHO-K1 cells. DP reduced the resistance of CHO-Adr(r) 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.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1981

Probability aspects of supernumerary production in the regenerating limbs of the axolotl, Ambystoma mexicanum.

The applicability of deterministic models, and in particular the polar co-ordinate model of French, Bryant & Bryant (1976), to the regenerative process has been investigated by performing ipsilateral blastemal rotations of varying angle on the fore and hind limbs of the axolotl. The results show that the frequency of supernumerary production rises with increasing angle to reach a peak at 180 degree and then falls off more rapidly, giving rise to an asymmetric distribution curve. The position of supernumerary outgrowth als suggests a probabilistic event, there being no consistent relationship between this parameter and the angle of rotation. The polar co-ordinate model is incapable of explaining these results and the work suggests that the determinism of current regeneration models may have to be abandoned in favour of a more stochastic theory.

Ambystoma mexicanum↗
PubMed1966

Discriminative echolocation in a porpoise.

Operant conditioning techniques were used to establish a discriminative echolocation performance in a porpoise. Pairs of spheres of disparate diameters were presented in an under-water display, and the positions of the spheres were switched according to a scrambled sequence while the blindfolded porpoise responded on a pair of submerged response levers. Responses which identified the momentary state of the display were food-reinforced, while those which did not (errors) produced time out. Errors were then studied in relation to decreased disparity between the spheres. As disparity was decreased, errors which terminated runs of correct responses occurred more frequently and were followed by longer strings of consecutive errors. Increased errors and disruption of a stable pattern of collateral behavior were associated. Since some sources of error other than decreased disparity were present, the porpoise's final performance did not fully reflect the acuity of its echolocation channel.

Animals↗