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H T Abelson

Publications and source records attributed to H T Abelson.

At least 37 records · Page 2Linked to original sources
PubMed1980

Natural resistance to methotrexate in human melanomas.

Human melanomas are naturally resistant to methotrexate (MTX). The mechanism of intrinsic drug resistance has been explored in 3 melanoma cell lines not previously exposed to this agent. All 3 lines exhibited relative MTX resistance with ID50 values of greater than 1 microM. Drug uptake studies were performed over an extracellular concentration range of 0.1 to 10 microM MTX. The uptake was linear over the initial 10 min at all concentrations and subsequently reached plateau levels only at the 10 microM concentration. Lineweaver-Burke transformations yielded apparent Km (uptake) values of 1.4 to 5 microM, similar to data obtained from other human cell lines. The level of dihydrofolate reductase (DHFR) in the human melanoma cells ranged between 8.42 to 11.98 pmoles/mg protein. The melanoma DHFR levels are several fold higher than in MTX-sensitive human tumor lines and up to a hundred-fold higher than that measured in human brain tumor cells by our assay. The intrinsic resistance of these melanoma lines has therefore been attributed to elevated intracellular levels of DHFR.

Drug Resistance↗
PubMed1979

Uncoupling of RNA and DNA synthesis after plasma stimulation of G0-arrested BALB/C-3T3 cells.

The addition of whole serum to G0-arrested, confluent Balb/c-3T3 cells induces them to progress through G1 and synthesize DNA after a 12-h lag period. Prior to the onset of DNA synthesis, RNA is synthesized and RNA content increases. Serum has been fractionated into two sets of growth factors: a platelet-derived growth factor present in heat-treated (100 degrees C) platelet extracts and platelet-poor plasma. Addition of whole serum, platelet-derived growth factor or platelet-poor plasma induces quiescent cells to increase their cytoplasmic RNA content, but the cells treated with platelet-poor plasma do not synthesize DNA. Messenger RNA content increases within 2 h after stimulation with whole serum or platelet-poor plasma, and after 18 h, mRNA has accumulated to a greater degree than rRNA.

Animals↗
PubMed1979

Identification of dihydropteridine reductase in human platelets.

Normal human platelets were shown to contain the enzyme dihydropteridine reductase. The enzyme was not found in a variety of other cells of hematogenous origin. Partial purification and kinetic and physical data indicated that the platelet enzyme is similar to that previously characterized from liver. Dihydropteridine reductase is important for the regeneration of tetrahydrobiopterin, a required cofactor in hydroxylation reactions involved in biogenic amine formation. The presence of the enzyme may indicate that some synthesis de novo of serotonin and/or catecholamines occurs in platelets, as opposed to a purely storage and transport function. In addition, screening for hyperphenylalaninemia due to dihydropteridine reductase deficiency may become feasible by assaying platelets for enzyme activity.

Blood Platelets↗
PubMed1978

Comparative effects of citrovorum factor and carboxypeptidase G1 on cerebrospinal fluid-methotrexate pharmacokinetics.

A comparison between citrovorum factor (CF) and carboxypeptidase G1 (CPDG1) rescue with respect to cerebrospinal fluid (CSF)-methotrexate (MTX) disappearance was studied in a patient with recurrent medulloblastoma who had a ventriculoperitoneal shunt. CPDG1 rescue resulted in a prolonged CSF-MTX half-life of 16.5-23 hours in comparison with CF rescue where the CSF-MTX half-life was 6.5-7.2 hours. There was a positive clinical response measured by loss of bone pain, increased physical activity, and almost complete clearing of CSF blast cells. CPDG1 rescue after high-dose MTX may provide more intense and selective treatment for meningeal neoplasms.

Adolescent↗
PubMed1978

Resistance of resting 3T6 mouse fibroblasts to methotrexate cytotoxicity.

We have compared the relative susceptibility of resting (GO) versus exponentially growing mouse fibroblasts (line 3T6) to methotrexate (MTX) cytotoxicity. Cultures of cells were exposed to different levels of MTX for various intervals. Cloning efficiencies of the cells were then determined in medium containing hypoxanthine and thymidine. We found that growing 3T6 cells exhibit time- as well as dose-dependent cytotoxicity. Greater than 95% of the cells were killed by a 24-hr exposure to 10(-6) M MTX. In contrast resting cells showed no loss of cloning efficiency even at drug concentrations of 10(-3) M and exposure times of 7 days. The resistance of resting cells is not the result of a MTX transport deficiency since extracellular MTX is taken up by both resting and growing cells. Furthermore, intracellular dihydrofolate reductase activity is abolished in both resting and growing cells at similar extracellular MTX dosages.

Cell Cycle↗
PubMed1977

The relative amounts of the cytoplasmic RNA species in normal, transformed and senescent cultured cell lines.

We have examined the relative quantities of 18S and 28S rRNA, 4S RNA and poly (A) + mRNA in the following cultured cells: the mouse fibroblast lines 3T3 and 3T6 in the resting (contact inhibited) and growing (sparse) states, 3T3 clones transformed with SV40 (SV3T3) and with both SV40 and polyoma SV-Py 3T3), hamster lung fibrobalsts (v79), human cervical carcinoma cells (HeLa), and human diploid fibroblasts at early and late passage. The relative quantities of the RNA species were determined by labeling the cells to equilibrium with 32PO4 and measuring the amount of label in each RNA species. The ratio of mRNA to rRNA varied form 1.1% to 2.7% in the different cell lines, the more rapidly growing cell lines usually giving a higher ratio. In cells experiencing growth limitation either by contact inhibition or due to senescence, the ratio of mRNA to rRNA was about 30% lower than in the corresponding cells in the growing state. In most cell lines the ratio of 4S RNA to 18S rRNA was between 0.8 and 1.2, but in seescent fibroblasts, this ratio increased to greater than 1.7. Senescent fibroblasts also contained much more total RNA per unit of DNA than the same cells at early passage or than 3T6 or 3T3 cells.

Animals↗
PubMed1977

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Amygdalin↗
PubMed1976

Changes in RNA in relation to growth of the fibroblast. IV. Alterations in theproduction and processing of mRNA and rRNA in resting and growing cells.

In previous reports, it was shown that both the concentration and rate of production of rRNA and mRNA were greater in growing than in resting 3T6 fibroblasts. Studies on isolated nuclei indicated that ribosomal RNA production is apparently controlled at the level of transcription. In contrast, hnRNA, the putative precursor of mRNA, appeared to be synthesized at the same rate in resting and growing cells. This finding was unexpected and has been tested in several ways. In this report, we show by an independent method that the relative rate of production of mRNA compared to hnRNA is several-fold higher in growing than in resting cells. However, the kinetics of processing of mRNA appear unchanged. This result suggests either that mRNA arises from a small subfraction of hnRNA or that the efficiency of processing of the hnRNA precursor is an important control mechanism which determines mRNA production ingrowing and resting states. Comparison of the initial rates of labeling of hnRNA and cytoplasmic message gives the efficiency with which the cytoplasmic mRNA is produced from nucleoplasmic RNA. The very low efficiency (3-4% in growing and 1-2% in resting cells) suggests that not every hnRNA molecule gives rise to a cytoplasmic message. In contrast to the similar kinetics of mRNA production in resting and growing states, processing of ribosomal RNA is much slower in the resting state and the emergence time for 28S RNA from nucleolus is greatly lengthened.

Cell Division↗
PubMed1975

Changes in RNA in relation to growth of the fibroblast. III. Posttranscriptional regulation of mRNA formation in resting and growing cells.

The proportion of hnRNA processed into cytoplasmic mRNA in resting and growing 3T3 and 3T6 cells has been investigated by measuring the efficiency of transfer of nuclear poly(A) to the cytoplasm. When nuclear poly(A) is either labeled continuously with precursor or pulse labeled and then chased with cordycepin, growing cells transfer approximately twice as much of the poly(A) from the nucleus to the cytoplasm as do resting cells. When cells undergo a serum-induced transition from the resting to growing state, the efficiency of poly(A) transfer is increased to that characteristic of growing cells by 3 hr after the addition of the serum. On the other hand, the proportion of hnRNA which is polyadenylated and the total nuclear poly(A) content are the same in resting and growing cells. It appears that the principal means by which the cell regulates its poly(A)+ mRNA content in the growing and resting states is by regulating the efficiency which nuclear poly(A)+ RNA is converted to cytoplasmic mRNA.

Adenine↗