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G P Tryfiates

Publications and source records attributed to G P Tryfiates.

At least 19 recordsLinked to original sources
PubMed1989

Biosynthesis of a novel form of vitamin B-6 by tumor cells.

Studies on the time-course utilization of radiolabeled pyridoxine in hepatoma-bearing rats led to the discovery of a novel vitamin B-6 product. It is present in a spectrum of tumor lines, but it is absent or occurs minimally in normal tissues. Hepatomas incorporate up to 20-30% of labeled pyridoxine into the novel species. Its structure was tentatively identified as adenosine-N6-methyl, propylthioether-N-pyridoximine-5'-phosphate. In the present study, 3B3 mouse-human hybridoma cells were incubated with radiolabeled precursor molecules, perchloric acid cell extracts were analyzed by high performance liquid chromatography (HPLC), and radioactivity in effluent fractions was measured. The results show that [G-3H]pyridoxine, [2,8-3H]adenosine, L-[35S]cysteine and L-[U-14C]serine are incorporated into the novel tumor product. These findings are interpreted to indicate that the correct structure of the novel product is adenosine-N6-diethylthioether-N'-pyridoximine-5'-phosphate. Further, these data demonstrate that tumor cells have evolved novel enzymatic steps for metabolism of vitamin B-6. The potential use of the novel metabolite as a marker for tumor genesis and establishment is especially significant, as the compound is peculiar to the neoplastic state.

Adenosine↗
PubMed1981

Effects of pyridoxine on serum protein expression in hepatoma-bearing rats.

The effect of pyridoxine depletion on the expression of serum protein species in control and Morris hepatoma No. 7777-bearing rats was studied with polyacrylamide gel electrophoresis (PAGE). A group of 20 Buffalo female rats was fed ad libitum a complete diet lacking pyridoxine, whereas a similar group was fed the same diet with pyridoxine. After a 22-day feeding period, 12 animals from each group were inoculated with hepatoma No. 7777 cells in the thigh muscles of both hind legs and allowed to grow for 25 days. Sera were obtained from all animals by heart puncture under light ether anesthesia, and protein species were resolved by PAGE. Eight and four protein bands in the haptoglobin and postalbumin regions, respectively, were resolved from control rat serum, whereas sera from depleted animals had eight and three bands, respectively. Protein expression was facilitated by the presence of hepatomas. Ten and six protein bands were seen in the haptoglobin and postalbumin regions, respectively, upon PAGE of sera from control tumor-bearing rats. A positive synergistic effect between pyridoxine lack and tumor presence was also found. Twelve and five bands were resolved in the haptoglobin and postalbumin regions, respectively, when sera from pyridoxine-depleted tumor-bearing rats were electrophoresed. These results showed that vitamin B6, in addition to its well-known coenzymatic function, exercised a type of control over protein expression, which may be positive or negative depending on the nutritional and health status of the animal.

Animals↗
PubMed1981

Vitamin B6 and cancer (review).

Vitamin B6 is required for normal growth and development, in general. The effect(s) of the vitamin on tumor growth, particularly of Morris hepatomas, and on metabolic function (i.e. enzyme activity) are herewith reviewed. Evidence is presented on the biochemical relationship(s) of pyridoxal 5'-phosphate with thymidylate synthetase and its inactivation by fluorodeoxyuridylate as well as of the therapeutic effects of direct treatment in situ with the antivitamin complexing agent L-penicillamine.

Animals↗
PubMed1978

Expression of hormonally induced tyrosine aminotransferase in host liver and Morris hepatoma No. 7777 during cofactor depletion.

Cytoplasmic tyrosine aminotransferase (L-tyrosine: 2-oxoglutarate aminotransferase, EC2.6.1.5) was partially purified from host liver and Morris hepatoma No. 7777 grown in pyridoxine depleted rats. The animals were sacrificed six hours following the intraperitoneal administration of hydrocortisone hemisuccinate. Enzyme preparations were subsequently resolved by electrophoresis on polyacrylamide gels. Enzyme activity was detected histochemically in situ on the gels. Six and at least three enzymatically active protein peaks were detected in host liver and the hepatoma, respectively, by this method.

Animals↗
PubMed1977

Effect of cofactor depletion on liver tyrosine aminotransferase expression.

Hepatic tyrosine aminotransferase (L-tyrosine: 2-oxoglutarate aminotransferase, EC 2.6.1.5) was partially purified from pyridoxine depleted and control rats and subsequently resolved by electrophoresis on polyacrylamide gels. Enzyme activity was detected histochemically in situ on the gel. Six enzymatically active forms were detected. Cofactor depletion effected further resolution of the enzyme into seven active forms as revealed by the bifurcation of the major active peak.

Animals↗
PubMed1976

Metabolism of pyridoxine in the liver of vitamin B-6-deficient rats.

The metabolism of [6-3H]pyridoxine - HCl was investigated in the liver of vitamin B-6-deficient rats. Rats were made vitamin B-6 deficient by feeding ad libitum for 42 days a diet lacking pyridoxine but otherwise optimal. Animals were each injected intraperitoneally with 33 muCi of [6-3H] pyridoxine - HCl and killed at different time intervals afterwards up to 7 days. Radioactively labeled hepatic B-6 compounds were extracted with acid and chromatographically separated on Dowex-X8 (H+) columns and the percent radioactivity for each vitamin compound was then calculated. Maximal uptake in control and deficient animals was observed 30 and 60 min, respectively, after administration of label. Radioactivity was not retained by the control animals but decreased steadily in a linear fashion after 30 min, reaching a low level after 3 h. On the other hand, vitamin deficient animals accumulated almost twice as much radioactivity in their liver as the controls and retained it through 7 days. In vitamin B-6 deficient animals 93% of the injected radioactivity was metabolized within 2 min at which time pyridoxine 5'-P and pyridoxal 5'-P reached 36 and 44% levels, respectively. Pyridoxine 5'-P dropped to minimal values (3%) within 15 min and remained unchanged for 7 days while pyridoxal 5'-P reached a peak (79%) level at 15 min and then began to drop linearly reaching a plateau (29%) at 5 days. Further, as the level of pyridoxal 5-P was falling, pyridoxamine 5'-P was linearly synthesized reaching a platuau low level (3%). The specific activity level of pyridoxal kinase decreased 3.2 times and that of pyridoxine 5'-phosphate oxidase increased 1.5 times in the state of deficiency. The results presented show that metabolism of [3H]pyridoxine in deficiency is characterized by (a) a delayed, two-fold increase in label uptake as well as an extended label retention period, (b) a rapid pyridoxal 5'-P synthesis, and (c) a continuous synthesis (and accumulation) of pyridoxamine 5'-P which is not utilized or further metabolized.

Aging↗
PubMed1976

Effect of pyridoxine on the growth of Morris hepatoma No. 7288Ctc and enzyme activity.

The effect(s) of lack of dietary pyridoxine (PX) on the growth of Morris hepatoma no. 7288Ctc was studied. Buffalo strain female rats were fed a diet lacking PX. Pair-fed controls were fed the same diet with PX added. Animals were inoculated with no. 7288Ctc hepatoma cells at 21 days and were sacrificed 16 days later. Host livers and tumors were removed, weights recorded and the activity of tyrosine aminotransferase (TAT; L-tyrosine: 2-oxoglutarate aminotransferase, EC 2.6.1.5) was determined in both host liver and hepatoma. The average weight of 30 hepatomas grown in pair-fed control rats was 11.61 +/- 1.5 g while the average weight of the same number of hepatomas grown in animals fed the PX free diet was 4.73 +/- 0.7 g (P less than 0.001). Further TAT specific activity levels were 39% and 32% higher in host livers and tumors from deficient animals, respectively. The results show that availability of dietary pyridoxine stimulates the growth of this hepatoma and, in addition, exercises a type of control over the expression of TAT activity.

Animals↗
PubMed1976

Expression of hormonally induced tyrosine transaminase in normal, host liver and three Morris hepatomas.

Cytoplasmic tyrosine transaminase (L-tyrosine: 2-oxoglutarate aminotransferase, EC 2.6.1.5) was partially purified from normal, host liver and three Morris hepatomas and subsequently resolved by electrophoresis on polyacrylamide gels. Enzyme activity was detected histochemically in situ on the gels. Seven enzymatically active forms were detected in normal liver. The presence of growing hepatomas altered significantly the expression of this enzyme. Only one, two and four activity peaks were detected in the host liver of animals with highly (most liver-like), well and poorly (least liver-like) differentiated hepatomas, respectively. Similarly, only one, four and six peaks were detected, respectively, in highly, well and poor differentiated hepatomas.

Animals↗
PubMed1975

The effect of retinol and retinoic acid on physiological and biochemical changes in retinol-deficient rats.

1. The effects of retinol and retinoic acid supplementation of retinol-deficient rats were studied for a variety of metabolic processes shown to be affected by retinol-deficiency. 2. Retinol-deficient rats were found to have decreased body-weight, liver and testes weights, a degeneration of testicular germinal cells, an increased incorporation of labelled choline into liver and testes phospholipids, an increased protein synthetic activity (in vitro) of liver ribosomes, an increased transfer-RNA methyltransferase activity in liver and a decreased activity in testes, an increased DNA content of testicular nuclei, and a decreased uptake of [3-H]thymidine by testicular nuclear DNA. 3. In retinol-deficient rats supplemented for 8 weeks with retinol these changes were reversed, measurements returning to control levels. 4. In retinol-deficient rats supplemented for 8 weeks with retinoic acid all changes were reversed except those in the testes. 5. Testicular signs of retinol deficiency appeared to be delayed when retinoic acid was added to the retinol-deficient diet of weanling rats. This suggests a sparing action of retinoic acid on the rat's utilization of retinol. 6. Suggestions are offered as to why retinoic acid will support growth and development but not spermatogenesis in the rat.

Animals↗
PubMed1975

Effect of pyridoxine availability on the activity of serine dehydratase of normal liver, host liver, and three Morris hepatomas.

The effect(s) of dietary pyridoxine availability on serine dehydratase (SD) specific activity levels of normal liver. Morris hepatomas "5123A, 7316B, 7800, and of respective host livers was studied. Buffalo female weanling rats were fed ad libitum a pyridoxine-free diet or the same diet supplemented with the vitamin. They were inoculated intramuscularly in the hind leg muscles with hepatoma cells after 3 weeks on the respective diets, and those bearing hepatomas "5123A, 7316B, 7800 were killed at 28, 30, and 48 days, respectively, after inoculation. SD activity was highly affected by pyridoxine. Absence of the vitamin from the diet resulted in greatly reduced activity levels in normal liver and the three hepatomas. Tumors grown in animals fed the pyridoxine-supplemented diet had 39j ("5123A), 3.5 ("7316B), and 2.1 ("7800) times more SD specific activity tan respective tumors grown in animals fed the deficient diet. A 1.7-fold increase was observed in normal liver. In contrast to these findings, the specific activity of the enzyme was reduced by 6.3, 1.5, and 3.0 times, respectively, in the host livers of animals fed the vitamin-supplemented diet and bearing hepatomas "5123A, 7316B, and 7800. Serine dehydratase activity depends greatly on dietary vitamin B6 and hence I propose that activity levels in vivo are regulated by its presence or absence.

Animals↗
PubMed1975

Hormonal induction of tyrosine aminotransferase activity in host liver and hepatoma no. 7777 of normal and cofactor-depleted animals.

Induction of tyrosine aminotransferase (TAT) (EC 2.6.1.5) by hydrocortisone was studied during cofactor (pyridoxal phosphate) depletion in hepatoma-bearing BUF strain female rats. Pairs of rats were matched for weight and age and one from each pair was fed ad libitum a diet lacking pyridoxine; the other (referred to as "pair-fed") was given the same diet supplemented with the vitamin, with the amount restricted to that consumed by the matched animal on the deficient diet. All animals were inoculated with Morris hepatoma no. 7777 cell after 21 days on the respective diets. TAT specific activity was determined weekly in host liver and hepatoma, in the presence and absence of cofactor, before and after the administration of hydrocortisone. Free and bound pyridoxal phosphate was estimated enzymatically. The average weight of hepatomas from pair-fed animals was 1.5-fold to twofold greater than that of hepatomas from animals on deficient diets. TAT activity of hepatomas was two times greater than that of host liver, and lack of dietary pyridoxine was without effect. Hormonal induction of enzymatic activity was maximal after the first week of tumor growth and subsequently reached minimal values. In pair-fed animals, tumor TAT was approximately 60% saturated with cofactor. In vitamin-deficient animals, only 6% of the tumor enzyme was saturated with the cofactor. The percent saturation of host liver TAT varied, with minimal values found in the vitamin-deficient animals. Hepatic and tumor pyridoxal phosphate content of pair-fed animals was unusually high (10 mug/g); in vitamin-deficient animals, only the coenzyme content of hepatomas was high (7.0 mug/g). The results showed that presence of the tumor altered the a) specific activity level of TAT and tissue content of cofactor, b) pattern of hormonal induction of the enzyme, and c) effects of the absence of dietary pyridoxine on TAT induction observed in animals without tumors.

Animals↗