Lymphosarcoma P1798 Research Articles

Effect of 9α-fluoroprednisolone and l-asparaginase on uridine incorporation into ribosomal RNA of P1798 lymphosarcoma

The effect of the lympholytic agents, 9α-fluoroprednisolone and l-asparaginase ( l-asparagine amidohydrolase, EC 3.5.1.1) from Escherichia coli (enzyme 2) on the incorporation of uridine into ribosomal RNA (rRNA) of P1798 lymphosarcoma was studied. After a 6- or 18-h treatment with either 9α-fluoroprednisolone or l-asparaginase, there was a marked decrease in incorporation into 18-S and 28-S rRNA. Incorporation into the 28-S component was significantly decreased 3 h after the administration of l-asparaginase, whereas 9α-fluoroprednisolone had no effect at this time. Neither 9α-fluoroprednisolone nor l-asparaginase depressed precursor incorporation in mice bearing steroid- or asparaginase-resistant tumors. These results suggest that changes in rRNA metabolism are related to tumor regression.

Effect of in vitro glucocorticoid treatment on acid ribonuclease activity in P1798 lymphosarcoma cells.

SummaryCell lines of P1798 lymphosarcoma which have been established in culture for more than 1 year exhibit corticoid sensitivity and growth characteristics similar to the parent, regular transplant when injected into host BALB/c mice. These cells also develop increased acid ribonuclease activity after incubation with 9a-fluoroprednisolone in vitro. The experiments described show that the increased ribonuclease previously reported is related to a direct action of the steroid on the cells.

Changes in ribonuclease activities in P1798 lymphosarcoma after asparaginase treatment

Alkaline and acid ribonuclease (RNase) are elevated in homogenates of P1798 lymphosarcoma 18 hours after in vivo treatment with l-asparaginase (EC-2). No change in the enzyme activities was observed 2 or 4 hours after treatment, and intermediate times were not used to determine the exact time of onset of this increased activity. Homogenates of both asparaginase-sensitive and -resistant tumors 18 hours after treatment were separated into three fractions by ammonium sulfate precipitation. The first two fractions contained both alkaline and acid RNase activities, and the third fraction had only acid RNase activity. All of the fractions from the sensitive tumor showed an increased activity after EC-2 treatment. Each fraction was subjected to DEAE-cellulose chromatography. The first as well as the third fraction yielded a single peak, while the second fraction was separated into two peaks of activity. The second peak, which was eluted with 0.15–0.20 m NaCl, contained the majority of the activated alkaline RNase, while the two peaks contained an equal amount of the activated acid RNase. The DEAE-cellulose chromatography also removed an inhibitor from the RNase (RNases).

Ribonuclease Inhibitor in Lymphosarcoma P1798: Effects of Steroid and 5-FU

SummaryAdministration of 5-fluorouracil (5FU) to animals bearing Strain II lymphosarcoma P1798 results in a decrease in activity of a ribonuclease inhibitor at 4 hours. This precedes by about 2 hours the increase in acid ribonuclease activity, and precedes by about 20 hours any measurable tumor regression. Treatment of this strain with 9α-fluoroprednisolone (9FP) had no effect on inhibitor activity. Treatment of Strain I tumors with 9FP which also leads to increased ribonuclease activity and tumor regression had no effect on the ribonuclease inhibitor, nor did treatment with 5FU in this strain. There was about half as much inhibitor activity present in controls of Strain I as in controls of Strain II.

Properties of a ribonucleate 2′-nucleotidohydrolase in a mouse lymphosarcoma

An enzyme which has ribonuclease activity has been purified approx. 200-fold from mouse lymphosarcoma P1798. This enzyme, a ribonucleate 2′-nucleotidohydrolase, hydrolyzes native RNA and pancreatic ribonuclease-predigested ‘core RNA’ to HClO 4-soluble products. Of the synthetic nucleotides tested, poly (U) is hydrolyzed most rapidly and is followed more slowly by poly (I) and poly (A). Poly (C) is very poorly hydrolyzed. Adenosine 2′,3′-phosphate is degraded most rapidly of the cyclic nucleotides, and if this rate is arbitrarily set at 100 %, the rates of cyclic GMP, UMP and CMP are 60, 25 and 18 % respectively. The product of adenosine 2′,3′-phosphate hydrolysis was identified as adenosine 2′-phosphate.

Effects of Corticoid Injection and of Adrenalectomy on in vitro Amino-acid Incorporation into Microsomes of P1798 Lymphosarcoma

Effects of Corticoid Injection and of Adrenalectomy on in vitro Amino-acid Incorporation into Microsomes of P1798 Lymphosarcoma

Cytolytic action of corticosteroids on thymus and lymphoma cells in vitro.

Mouse and rat thymus cells can be maintained in good condition for up to 24 hours in tissue culture medium (Fischer's or 199) with serum or serum proteins, when aerated and incubated at 38 °C in stoppered tubes. Addition of corticosteroids produces cytolytic effects in nearly all cells, which are highly specific for those compounds having an 11β-hydroxyl group. Maximum effect occurs at concentrations of cortisol 0.27 μM, of dexamethasone 0.02 μM. Electron microscopy shows marked alteration at 2 hours with nuclear edema and disappearance of the normal chromatin pattern in treated cells, progressing to maximum at about 8 hours with disruption of nuclear and cell membranes. Steroid-sensitive mouse lymphosarcoma P1798 cells show similar changes, whereas those of the steroid-resistant subline do not. To demonstrate this action of corticosteroids at concentrations that are significant physiologically, the major difficulty is maintaining the cells in satisfactory condition. It is concluded that this effect of steroids is manifested only in cells that are intact and metabolically active, and might be independent of many other known biochemical changes produced by corticosteroids.

Inhibition of 11β-Hydroxysteroid Dehydrogenase Activity in Rat and Mouse Tissuesin Vitroandin Vivo

Dehydrogenation of the 11β- hydroxyl group of cortisol to form cortisone proceeded most rapidly in vitro in kidney tissue of mice and rats; spleen, thymus and lymphosarcoma of mice were less active, while skeletal muscle and tumor stroma of mice and rats and rat thymus reticular tissue showed low activity. Dehydrogenation was inhibited considerably by 11-epi-cortisol, 11-epi-prednisolone and llα-hydroxyprogesterone in concentrations up to 9 times that of cortisol (9XF). Renal vein blood collected after injection of cortisol-4-l4C contained cortisone, and simultaneous injection of inhibitors (up to 11XF) reduced the ratio cortisone/cortisol from 0.19 to 0.09 in mice and from 0.14 to 0.06 in rats. Inhibitors (4XF) injected subcutaneously enhanced 2-fold the involutionary effect of standard doses of cortisol and prednisolone on mouse thymus, which contains considerable enzyme activity, but not rat thymus, which contains little. Growth of steroid-resistant mouse lymphosarcoma P1798 was not affected by compoun...

VINBLASTINE EFFECT ON NUCLEIC ACIDS AND RIBONUCLEASE OF LUMPHOID TISSUE.

SummaryThe RNA concentration and ribonuclease activity in rat thymus were decreased by injection of vinblastine. The same results were noted in both the corticoid sensitive and resistant strains of mouse lymphosarcoma P1798. An apparent increase in DNA concentration was noted in rat thymus and corticoid-sensitive P1798. No change in DNA concentration was noted in the corti-coid-resistant tumor.

The metabolism in vitro of [4- 14C]cortisone by lymphosarcoma P1798

The metabolism in vitro of [4- 14C]cortisone by homogenates of cortisone-sensitive and resistant lines of lymphosarcoma P1798 was studied. The administration of cortisol for several days to mice bearing these tumors significantly altered the capacity of both tumor lines to metabolize cortisone. Following such treatment, the cortisone-sensitive tumor appears to be more efficient in converting cortisone to cortisol, while the resistant neoplasm is better able to convert cortisone to 20β-hydroxycortisone ( Reuchstein's substance “U”) which is biologically inactive. The results suggest that the enzymes which mediate the formation of these metabolites may be responsive to glucocorticoid administration.