Abstract By grafting spontaneous leukemia tumor cells, the myeloid My2/De leukemia rat model was established. Death was caused by impaired functions of heavily infiltrated organs. In vitro culturing ...of tumor cells, blood and bone marrow counts and cytochemic reactions indicated the leukemic the origin resembling human myeoloblastic leukemia. Metastatic spread was followed after i.v. and i.p. injection, and by implantation of leukemia cells under the renal capsule of rats. Primary tumor and metastasis formation was visualized by18 FDG or11 C-methionine administration and MiniPET. The accumulation of radiotracers was measured in different organs and expressed as Differential Absorption Ratios (DARs). Subrenal implantation of My2/De cells resulted in their appearance in other abdominal organs and in parathymic lymph nodes. The release of tumor cells from the primary kidney to the peritoneum was mimicked by the i.p . administration of ink particles. Ink particles deposited in the abdominal organs and in the thoracal lymph nodes, preferentially in parathymic lymph nodes, confirming the notion of lymphatic spread of metastasis.
Myalgia and muscle weakness may appreciably contribute to the poor adherence to statin therapy. Although the pathomechanism of statin-induced myopathy is not completely understood, changes in calcium ...homeostasis and reduced coenzyme Q
10
levels are hypothesized to play important roles. In our experiments, fluvastatin and/or coenzyme Q
10
was administered chronically to normocholesterolaemic or hypercholaestherolaemic rats, and the modifications of the calcium homeostasis and the strength of their muscles were investigated. While hypercholesterolaemia did not change the frequency of sparks, fluvastatin increased it on muscles both from normocholesterolaemic and from hypercholesterolaemic rats. This effect, however, was not mediated by a chronic modification of the ryanodine receptor as shown by the unchanged ryanodine binding in the latter group. While coenzyme Q
10
supplementation significantly reduced the frequency of the spontaneous calcium release events, it did not affect their amplitude and spatial spread in muscles from fluvastatin-treated rats. This indicates that coenzyme Q
10
supplementation prevented the spark frequency increasing effect of fluvastatin without having a major effect on the amount of calcium released during individual sparks. In conclusion, we have found that fluvastatin, independently of the cholesterol level in the blood, consistently and specifically increased the frequency of calcium sparks in skeletal muscle cells, an effect which could be prevented by the addition of coenzyme Q
10
to the diet. These results support theories favouring the role of calcium handling in the pathophysiology of statin-induced myopathy and provide a possible pathway for the protective effect of coenzyme Q
10
in statin treated patients symptomatic of this condition.
The distinguishable morphologic features of nuclei of acute myelogenous leukemia cells with enlarged size and finely distributed nuclear chromatin indicate incomplete chromosome condensation that can ...be related to elevated gene expression. To confirm this, interphase chromosome structures were studied in exponentially growing rat myelomonocytic leukemia 1 cells isolated at the University of Debrecen (My1/De cells). This cell line was established from primary rat leukemia chemically induced by 7,12-dimethylbenzaanthracene treatment. The enlarged nuclei of My1/De cells allowed improved fluorescent visualization of chromosomal structures. Increased resolution revealed major interphase intermediates consisting of (1) veil-like chromatin, (2) chromatin ribbon, (3) chromatin funnel, (4) chromatin bodies, (5) elongated prechromosomes, (6) seal-ring, spiral shaped, and circular chromosomal subunits, (7) elongated, bent, u- and v-shaped prechromosomes, and (8) metaphase chromosomes. Results confirmed the existence of the chromatin funnel, the first visible interphase chromosome generated by the supercoiling of the chromatin ribbon. Other intermediates not seen previously included the spiral subunits that are involved in the chromonemic folding of metaphase chromosomes. The existence of spiral subunits favors the helical coil model of chromosome condensation. Incomplete chromatin condensation in leukemia cells throughout the cell cycle is an indication of euchromatization contributing to enhanced gene expression and is regarded as a leukemic factor.
Myalgia and muscle weakness may appreciably contribute to the poor adherence to statin therapy. Although the pathomechanism of statin-induced myopathy is not completely understood, changes in calcium ...homeostasis and reduced coenzyme Q^sub 10^ levels are hypothesized to play important roles. In our experiments, fluvastatin and/or coenzyme Q^sub 10^ was administered chronically to normocholesterolaemic or hypercholaestherolaemic rats, and the modifications of the calcium homeostasis and the strength of their muscles were investigated. While hypercholesterolaemia did not change the frequency of sparks, fluvastatin increased it on muscles both from normocholesterolaemic and from hypercholesterolaemic rats. This effect, however, was not mediated by a chronic modification of the ryanodine receptor as shown by the unchanged ryanodine binding in the latter group. While coenzyme Q^sub 10^ supplementation significantly reduced the frequency of the spontaneous calcium release events, it did not affect their amplitude and spatial spread in muscles from fluvastatin-treated rats. This indicates that coenzyme Q^sub 10^ supplementation prevented the spark frequency increasing effect of fluvastatin without having a major effect on the amount of calcium released during individual sparks. In conclusion, we have found that fluvastatin, independently of the cholesterol level in the blood, consistently and specifically increased the frequency of calcium sparks in skeletal muscle cells, an effect which could be prevented by the addition of coenzyme Q^sub 10^ to the diet. These results support theories favouring the role of calcium handling in the pathophysiology of statin-induced myopathy and provide a possible pathway for the protective effect of coenzyme Q^sub 10^ in statin treated patients symptomatic of this condition.
The ultimate cause of cancer death is, in most cases, the appearance of metastases. The aim of the present study was to contribute to animal experimental investigations of metastatic tumor ...development.
Rat hepatocarcinoma (He/De), mesoblastic nephroma (Ne/De) cells, and in other cases tumor-bearing lymph nodes were transplanted under the renal capsule of F344 rats. Metastatic potential of tumor cells was examined by whole body autoradiography and phosphor image analysis. The organ distribution of cells was also investigated.
Transplanted tumor cells resulted in metastases in the parathymic lymph nodes. Implanted India ink also demonstrated connection between the lymphatic vessels of the renal capsule and the parathymic lymph nodes. The metastatic potential was independent of the primary tumor growth rate.
The renal capsule-parathymic lymph node complex seems to be suitable for the isolated in vivo examination of metastatic development and for the detailed analysis of secondary tumors.
Different Percoll density gradients were used to purify granulocytes from Long-Evans, Fischer, Sprague-Dawley, and Fischer/Long-Evans hybrid rats. Three different discontinuous gradient types were ...developed which permitted the separation of polymorphonuclear leukocytes (PMNLs) from the peripheral blood of the different rat strains. Our purification techniques were compared to each other in terms of purity and yield. Purities of 97.7 +/- 0.6%, 97.0 +/- 1.1%, 96.4 +/- 1.2% and 96.7 +/- 1.1% were achieved for the granulocyte fractions of LE, F344, SD and FL/F1 rats, respectively. The superoxide production of the isolated cells was also investigated and it was established that the granulocytes could be activated by phorbol-12-myristate-13-acetate (PMA).
In our experiments we compared the serum lipoprotein lipid composition of Fischer 344 (F344) and Long-Evans (LE) inbred rats as well as of their hybrid FLF(1) from both sexes after feeding them for ...2, 4 and 8 weeks with different diets. The following diets were used: 1) standard diet marked as CRLT/N; 2) diet reach in butter marked as BR; 3) diet containing cholesterol, sodium cholate and methylthiouracil marked as CR; 4) diet marked as BRC, which is the Hartroft-Sós diet modified by our research group consisting of the diets BR and CR. The latter diet was the most effective, because within two weeks the level of serum total cholesterol, LDL-cholesterol, HDL-cholesterol and triglyceride in the F344 female rats increased 8, 30, 4 and 8 times, respectively. The male rats of the Long-Evans strain showed moderately increased values while the FLF(1) female hybrids derived from the hybridization of LE males and F344 females had values closer to those of the mother strain. Despite the fact that during this time the LDL/HDL ratio increased from 0.06 to 2.97 and the PON-1 activity decreased to one-third, a significant lipid deposition could not be shown in the wall of the abdominal aorta even two months later. Our experimental model is suitable for the chemoprevention of dyslipidaemia or rapid testing of molecules chosen for its treatment.
Fluvastain (Flu) is widely accepted to have anticancer effect although its in vivo chemopreventive ability in cancer has not been studied. The therapeutic and chemopreventive effects of Flu were ...compared in vivo in the present study.
Under the left renal capsule of FLF1 hybrid rats 10(6) hepatocarcinoma cells were implanted (He/De14) on sponge disc. The differences in net weight between the left and right kidneys were determined as tumor weights. Flu was administered per os in 0.5, 2 and 20 mg/kg/day doses.
The 21-day pretreatment before tumor implantation with Flu had no effect on tumor development in the absence of Flu treatment after the implantation. The addition of Flu before and after tumor implantation demonstrated a more intensive anticancer effect than in the case of treatment given only after tumor implantation.
Flu has in 0.5-20 mg/kg/day doses a therapeutic and also a preventive effect on hepatocarcinoma growth in rats depending on the type of administration.
Curcumin, the dietary pigment responsible for the yellow color of curry, has been reported to be a potent inhibitor of tumor promotion in mouse epidermis. Since most tumor promoters inhibit cell-cell ...communication, we have examined the effect of curcumin on the reduction of gap junctional intercellular communication induced by the phorbol ester phorbol-12,13-dibutyrate (PDBu) in BALB/c 3T3 cells. Treatment of cells with 50 microM curcumin slightly inhibited the dye coupling evaluated by intercellular transfer of a fluorescent dye Lucifer Yellow CH; however, lower concentrations of curcumin did not affect the level of intercellular communication. Addition of 200 nM PDBu caused a rapid reduction of dye coupling, which was not altered by either pretreatment or simultaneous curcumin addition.
A new, chemically induced animal tumor cell line (HeDe) was established and characterized by its property of causing aggressively growing tumors in specific strain of rats and changes in the ...chromatin structure. Results show that (1) the nuclear material in nuclei of normal resting (G0) hepatocytes consists mainly of decondensed veil-like chromatin, chromosomes being clustered in six lobular domains; (2) nuclei of HeDe cells contain primarily supercoiled chromatin; or (3) the nuclear material of tumor cells undergoes apoptosis seen as apoptotic bodies. Heterogeneity of chromatin structures was expressed as contour/area ratio and was nine times higher in apoptotic cells and two times higher in tumor cells compared to resting cells.
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