Comparative studies on the covalent binding of the carcinogen benzo(a)pyrene to DNA in various model systems.

The covalent binding of tritiated benzo(a)pyrene (BP) to DNA has been determined in rat liver in vivo, in rat liver perfused in situ, after incubation of BP with liver single cells, with liver homogenate, with liver microsomes and DNA, with fibroblasts from a rat granuloma pouch, and with 2 cell lines. Liver single cells were found to be a valuable compromise between the most sensitive system (microsomal incubation of BP and DNA) and the biologically most relevant system (in vivo).     

Hepatocellular injury inhibits lectin-mediated tumor colonization into BALB/c-mice livers

Acute (hepatitis) and chronic (cirrhosis) liver injuries were experimentally induced in BALB/c-mice by administration of D-galactosamine and carbon tetrachloride, respectively. In both experimental liver diseases the incidence of hepatic tumor colonization of sarcoma L-1 was significantly reduced as compared to non-treated control animals. Thus, it seems that either dysfunction or loss of organ-characteristic lectins (galactosyl-specific hepatic lectins) prevented liver colonization. Histochemical staining of liver sections from D-galactosamine or carbon tetrachloride-treated mice with appropriate galactose-containing (neo) glycoproteins supported this hypothesis, since the lectin-dependent binding was greatly reduced as compared to sections from non-treated animals.     

Immunohistochemical localization of glutamine synthetase in human liver

Glutamine synthetase (GS) of human liver was recognized with a polyclonal antibody to pig brain GS, but failed to stain with an antibody against rat liver GS. Using the latter antibody GS of human liver was shown to be localized within small rings of 1 to 3 hepatocytes surrounding the terminal hepatic venules. This pattern was analogous to that seen in rat and mouse liver.     

Comparative studies on the covalent binding of the carcinogen benzo(a)pyrene to DNA in various model systems

Summary The covalent binding of tritiated benzo(a) pyrene (BP) to DNA has been determined in rat liver in vivo, in rat liver perfused in situ, after incubation of BP with liver single cells, with liver homogenate, with liver microsomes and DNA, with fibroblasts from a rat granuloma pouch, and with 2 cell lines. Liver single cells were found to be a valuable compromise between the most sensitive system (microsomal incubation of BP with DNA) and the biologically most relevant system (in vivo).Presented in part at the 10th Annual Meeting of the Union of Swiss Societies of Experimental Biology, Experientia34, 925 (1978), abstract.Acknowledgment. We thank Dr G. Kistler, Institute of Anatomy, University of Zurich, for generously supplying the SIRC and VERO cell lines, and Mr P. Manser for the preparation of the granuloma pouch fibroblasts.     

Ascorbic acid biosynthesis in the mammalian kidney

The egg-laying mammals (Prototheria) synthesize L-ascorbic acid only in kidney, as is characteristic of reptiles. Bandicoots (Marsupialia) synthesize it in both kidney and liver. 2 other species of marsupials (kangaroos) synthesize it primarily in liver, but some individuals also synthesize in kidney.     

Immunohistochemical localization of glutamine synthetase in human liver

Glutamine synthetase (GS) of human liver was recognized with a polyclonal antibody to pig brain GS, but failed to stain with an antibody against rat liver GS. Using the latter antibody GS of human liver was shown to be localized within small rings of 1 to 3 hepatocytes surrounding the terminal hepatic venules. This pattern was analogous to that seen in rat and mouse liver.     

The absence of an inhibitory effect of metyrapone (2-methyl-1,2-di (3-pyridyl) propan-1-one) on hepatic microsomal hydroxylation in scurvy.

Microsomes from livers of scorbutic guinea-pigs showed a reduced rate of acetanilide hydroxylation. The response of "scorbutic" liver microsomes to the inhibitor Metyrapone (2-methyl-1,2 di (3-pyridyl) propan-1-one) was different from that of liver microsomes from non-scorbutic guinea-pigs.     

Acetyl-L-carnitine treatment stimulates oxygen consumption and biosynthetic function in perfused liver of young and old rats

The effect of treatment with acetyl-L-carnitine on hepatic mitochondrial respiration and biosynthetic function in perfused liver from young (90 days) and old (22-24 months) rats was studied. Rats were given a 1.5% (w/v) solution of acetyl-L-carnitine in their drinking water for 1 month and oxygen consumption together with the rate of gluconeogenesis, urea synthesis, and ketogenesis with and without added substrates were measured in perfused liver. Mitochondrial oxygen consumption was also assessed in liver homogenate and isolated mitochondria to determine the maximal capacity for oxidative phosphorylation. Acetyl-L-carnitine treatment almost completely restored the age-dependent decline in oxygen consumption, gluconeogenesis, urea synthesis, and ketogenesis found in perfused liver of old rats to the levels found in young rats. In addition, acetyl-L-carnitine treatment increased oxygen consumption and biosynthetic function in perfused liver from young rats. After acetyl-L-carnitine treatment, we found detectable 3-oxoacyl-CoA-transferase activity associated with a consumption of ketone bodies in young and old rats. Finally, oxygen consumption measured in homogenate and isolated mitochondria did not change with age and acetyl-L-carnitine treatment. Our results show that in perfused liver, acetyl-L-carnitine treatment slows the age-associated decline in mitochondrial respiration and biosynthetic function. In addition, treatment of young rats with acetyl-L-carnitine has a stimulating effect on liver metabolism, probably through an increase in ATP production. Received 25 October 2000; received after revision 14 December 2000; accepted 11 January 2001     

Effects of cycloheximide on protein synthesis in human lung tumors, regenerating rat liver and hepatomas

10(-4) M cycloheximide (CHM) inhibits leucine incorporation to about the same degree in slices of human lung tumors, rat hepatomas, regenerating livers and normal tissues. At 10(-6) M, CHM has a more pronounced effect on tumor tissue and regenerating liver than on normal tissues. 10(-8) M CHM stimulates protein synthesis in normal rat liver slices.     

Effect of sodium octanoate on leucine incorporation into protein of rat liver slices and of Yoshida ascites hepatoma cells.

7.38 X 10(-4) M octanoate does not significantly modify leucine incorporation into protein of rat liver slices, while in hepatoma cells a 19% inhibition has been noted. 3.69 x 10(-3) M octanoate reduces leucine incorporation to about the same extent (71-76%) in both liver slices and hepatoma cells.     

The role of maternal parathyroids and vitamin D3 metabolites in fetal growth and the deposition of glycogen reserves in the maternal and fetal liver in rats]

Thyro-parathyroidectomy of pregnant Rats at 12.5 days of gestation decreased maternal liver glycogen on 21.5 days of gestation and fetal weight as well as fetal liver glycogen stores. The graft of one parathyroid gland or the injection of 1 alpha-hydroxycholecalciferol in these thyro-parathyroidectomized mothers increased their liver glycogen stores at 21.5 days of gestation. These treatments also markedly increased both fetal weight and fetal liver glycogen stores. It was concluded that maternal 1,25-dihydorxycholecalciferol, which is synthesized under the control of parathyroid hormone secretion, controls fetal growth and liver glycogen stores. The mechanism of these effects (direct or indirect) requires further investigations.     

Effect of latent iron deficiency on the levels of iron, calcium, zinc, copper, manganese, cadmium and lead in liver, kidney and spleen of growing rats

Feeding a marginally low iron content diet (18-20 mg iron/kg diet) to weaned (21-day-old) rats for 8 weeks produced a significant decrease in liver non-heme iron (66%, p less than 0.001) but no change in blood hemoglobin. Total iron contents of liver (56%, p less than 0.01), spleen (20%, p less than 0.05), and kidney (19%, p less than 0.05) were also found to decrease along with increased zinc, copper, calcium, manganese lead and cadmium in various organs. The magnitude of alteration of a metal was different in different organs. However, liver was found to be the most affected organ. Two weeks of rehabilitation with iron-sufficient diet (390 mg iron/kg diet) normalized these altered levels.     

Effect of latent iron deficiency on the levels of iron,calcium, zinc,copper, manganese,cadmium and lead in liver,kidney and spleen of growing rats

Summary Feeding a marginally low iron content diet (18–20 mg iron/kg diet) to weaned (21-day-old) rats for 8 weeks produced a significant decrease in liver non-heme iron (66%, p<0.001) but no change in blood hemoglobin. Total iron contents of liver (56%, p<0.01), spleen (20%, p<0.05), and kidney (19%, p<0.05) were also found to decrease along with increased zinc, copper, calcium, manganese lead and cadmium in various organs. The magnitude of alteration of a metal was different in different organs. However, liver was found to be the most affected organ. Two weeks of rehabilitation with iron-sufficient diet (390 mg iron/kg diet) normalized these altered levels.     

Effects of sera and liver extracts from partially hepatectomized rats on liver slice DNA synthesis

Summary Sera from partially hepatectomized rats (PH) compared to sera from control rats (C) enhance liver slice DNA synthesis but depress kidney slice DNA synthesis. Alone, liver extracts from PH do not affect DNA synthesis; but adding sera to PH extracts stimulates, suggesting that sera and liver factors from PH may participate in compensatory growth.Acknowlegments. Supported by NIH, grant AM 15458, a grant from the Washington Heart Association, and Public Health Service, grant RR 5360 (Medical). The authors wish to express their appreciation to Angelina Vasques for technical assistance and Betty Mendelson, Patti Werr and Susan Dreux for secretarial help.     

Oyster mushroom (Pleurotus ostreatus) reduces the activity of 3-hydroxy-3-methylglutaryl CoA reductase in rat liver microsomes

The effect of dried oyster mushroom (Pleurotus ostreatus) on cholesterol (C) content in serum, in lipoproteins and in liver, and on the activity of 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase in liver microsomes, was studied in male rats (strain Wistar, initial body weight 75 g) fed on low-cholesterol (9 mg/100 g) and high-cholesterol (0.3%) diets. Addition of 5% oyster mushroom to both diets reduced significantly the C-content in serum (by 30%), in very-low- and low-density lipoproteins (in a 11 ratio to the decrease of total serum C) and in liver (by 50%), as well as the activity of HMG-CoA reductase (by more than 30%).     

On urea formation in marine mammals

Summary Ornithine carbamoyltransferase (EC 2.1.3.3) has been determined in homogenates of liver of the sei whale (Balaenoptera borealis), the bottle-nose dolphin (porpoise) (Tursiops truncatus) and California sea lion (Zalophus californianus). These marine mammals show levels of this ornithine-urea cycle enzyme which are typical of terrestrial mammals.Publication No. 12 from the Laboratory of Biochemical Ecology. Contribution No. 469, College of Fisheries, University of Washington. The authors are indebted to Allen Wolman of the Marine Mammal Laboratories (NOAA, Seattle) for the whale liver and to. J. Thomas Whitman, now of the Buffalo Zoological Gardens, for liver of the dolphin and sea lion. The experiments were conducted in the Department of Biochemistry and Nutrition, University of Texas Medical Branch, Galveston, Texas.     

Effect of thyroid hormone on somatomedin-C release from perfused rat liver

The effect of thyroid hormone on plasma somatomedin-C (SmC) level and on SmC release from perfused rat liver was investigated. Plasma SmC levels and liver tissue SmC were significantly increased in thyroxine-treated rats. Physiological doses of triiodothyronine increased SmC release and SmC concentration in the perfused rat liver. These results indicate that thyroid hormone directly enhances the synthesis and release of SmC in the rat.     

Evidence for synergism in steroid hormone-receptor association

Summary A number of glucocorticoids stimulated oestradiol binding to liver cytosol receptor; oestradiol activated glucocorticoid receptor association at a time when it reversed triamcinolone mediated increase in liver glycogen synthesis.These studies were supported by the DRGST (IMB 7570744), the INSERM (CL 7650014) and the CNRS (AI 03 1917).     

Die Wirkung der Temperatur auf das Verhalten der Gewebsatmung poikilothermer und homoiothermer Tiere unter dem Einfluss von 4,6-Dinitro-o-kresol

Summary (1) The liver respirationin vitro of mice and toads was studied under the influence of 4,6-Dinitro-o-cresol at temperatures varying from 17,5 to 42,5°C.(2) The percentage activity of the oxygen uptake of the mouse liver decreased progressively under dinitrocresol with rising temperatures, whereas the respiration of the toad liver showed inhibition at low temperatures and activation at higher temperature.(3) The results were interpreted following the theory of inhibitory types ofJohnson.