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R Schulte-Hermann

Publications and source records attributed to R Schulte-Hermann.

At least 127 records · Page 7Linked to original sources
PubMed1979

The regulative role of food consumption in the induction of rat liver cell proliferation by drugs and environmental pollutants.

alpha-hexachlorocyclohexane (alpha-HCH) was used to stimulate cell proliferation in rat liver. Food consumption at two different stages of the replicative cycle was found to be required for the enhancement of DNA synthesis by this agent: (1) Before or at the time of alpha-HCH administration (G0), (2) 12--15 hours later, i.e. 5--8 hours before initiation of DNA synthesis ("R"-point). Other alpha-HCH mediated changes in the liver i.e. organ enlargement and the induction of drug-metabolising enzymes, remained unaffected by the absence of food. This suggests that the nutritional control is specific for induction of DNA synthesis. It is concluded that food consumption, in addition to specific stimuli of liver growth, is an exogenous regulator of liver cell proliferation.

Animals↗
PubMed1977

Effect of hypophysectomy on the stimulation of liver growth by alpha-hexachlorocyclohexane, phenobarbital, and partial hepatectomy in the rat.

alpha-Hexachlorocyclohexane (alpha-HCH) or phenobarbital (PB) elicit growth and cell multiplication in rat liver. In hypophysectomized rats, alpha-HCH and PB induce an increase in liver mass, but no increase in liver DNA. Hypophysectomy without additional treatment results in a decrease of liver size and RNA, while the DNA content remains unchanged, thereby leading to a relative DNA surplus. 1/3-hepatectomy in hypophysectomized animals leads to a small increase of hepatic DNA only; after 2/3-hepatectomy 75-80% of the original liver DNA are restored. In rats with intact hypophysis losses of liver DNA are known to be restored completely. The findings suggest that the relative DNA surplus in hypophysectomized rats prevents the stimulation of DNA synthesis by weak growth stimuli such as alpha-HCH, PB, and 1/3-hepatectomy. If the relative DNA surplus is eliminated by partial hepatectomy, the inducers do produce DNA multiplication. It is concluded that the induction of liver growth and cell multiplication by alpha-HCH and PB does not require the presence of the hypophysis or one of its hormones.

Animals↗
PubMed1977

Two-stage control of cell proliferation induced in rat liver by alpha-hexachlorocyclohexane.

Determinants of the timing of DNA synthesis in rat liver were studied, using alpha-hexachlorocyclohexane as a tool for stimulation of cell proliferation. One determinant is the time of alpha-hexachlorocyclohexane administration. The increase in DNA synthesis starts after a lag phase (prereplicative phase) of minimally 20 hr. Use of animals adapted to a controlled feeding and lighting schedule revealed a second determinant provided by food consumption. Initiation of DNA synthesis is suppressed by fasting or protein deprivation and occurs 5 to 8 hr after readministration of a protein-containing diet. The light-dark rhythm has no direct influence on the timing of DNA synthesis. Stimulation of hepatic DNA synthesis, therefore appears to require two different sequential signals. The first is provided by alpha-hexachlorocyclohexane, and the second is provided by protein intake. In the absence of the second signal, committed cells are arrested at a critical point of the prereplicative phase and accumulate. Protein intake permits release from the block, and the accumulated cells enter the S period almost synchronously after completion of the remaining 5 to 8 hr of the prereplicative phase. These observations provide a means of synchronizing, in the living animal, a proliferating population of hepatocytes. In addition, they offer an explanation for the diurnal rhythmicity in the rate of hepatic cell proliferation.

Animals↗
PubMed1976

[Feeding rhythms and the diurnal rhythm of cell proliferation in pharmacologically induced liver growth (author's transl)].

Stimulation of hepatic DNA synthesis can be achieved in the intact rat by alpha-hexachlorocyclohexane (alpha-HCH = alpha-benzene hexachloride). The extent of stimulation is high in the morning and low in the evening. These rhythmic variations in the rate of DNA synthesis are synchronized indirectly by the light-dark rhythm, but directly by the animal's feeding habits: Rats eat preferentially during the night. If the diurnal rhythm of food intake is abolished, the rhythmic fluctuations in the rate of DNA synthesis are no longer detectable; if rats are adapted to daily feeding periods of only 5 h, these fluctuations are pronounced and almost synchronized. Further experiments show that the time of feeding determines the time of DNA replication. It is concluded that food intake provides a "2nd stimulus" or permissive factor, which is required for the induction of DNA synthesis in a certain critical stage of the prereplicative phase. Labelling experiments with orotic acid suggest that foot intake initially induces an increase of RNA synthesis. The results indicate that controlled feeding schedules provide the possibility to synchronize, in the living animal, a proliferating population of hepatocytes. A hypothesis is derived which offers an explanation for the generation of the diurnal rhythm of cell proliferation in the liver.

Animals↗
PubMed1976

Stimulation of cell proliferation in rat liver by alpha-hexachlorocyclohexane or partial hepatectomy and end points during G1 of the inhibitory action of beta-diethyl-aminoethylphenyldiallyl acetate-HC1 (CFT 1201), beta-diethylaminoethyldiphenylpropyl acetate. HC1 (SKF 525-A) and actinomycin D.

The present work was designed to study the nature, sequence and temporal position of some inhibitor-sensitive events of the replicative cycle in rat liver. Hepatocyte proliferation was induced by alpha-hexachlorocyclohexane and by partial hepatectomy; the onset of DNA synthesis and of mitotic activity were determined and used as reference points in the cell cycle. Inhibition of cell proliferation was achieved by CFT 1201, SKF 525-A, and actinomycin D. It was found that the inhibitory action of the three agents ends at the same stage of the replicative cycle, 0--2 h before the G1/S transition, in both alpha-hexachlorocyclohexane-stimulated and regenerating rat liver. It is concluded that the molecular events sensitive to CFT 1201, SKF 525-A or actinomycin D are either identical or temporally closely associated; they do not figure in the metabolic activation of alpha-hexachlorocyclohexane.

Cell Division↗
PubMedDate not supplied

Active cell death: role in hepatocarcinogenesis and subtypes.

Active cell death, the genetically programmed self-destruction of a cell, is now recognized to be a widespread phenomenon in biology that counterbalances mitosis to preserve tissue homeostasis. It is subject to the control of the growth regulatory networks in tissues. Close examination of the morphology of dying cells in liver and other tissues suggests that there are a number of morphological types of active cell death, ranging from forms dominated by nuclear changes and without signs of autophagy ("classical" apoptosis), e.g., in thymocytes and the liver, to those dominated by autophagic degradation of cytoplasm, e.g., in the mammary gland. The induction of gene expression in these diverse types of cell death is anticipated to be different. Here we review the data regarding the regulation of apoptosis in the liver by liver tumor promoter, transforming growth factor beta-1 and related peptides as well as nutrition. In the course of hepatocarcinogenesis, initiated cells as well as preneoplastic and neoplastic cell populations showed enhanced cell replication, but also enhanced apoptosis. Tumor promoter shift the balance between birth and death by increasing the rate of cell replication and by decreasing the rate of apoptosis. Thereby, liver tumor formation is accelerated. Food restriction exhibits the opposite effect and consequently, provides protection from carcinogenesis.

Animals↗
PubMedDate not supplied

Kinetics of apoptosis and secondary necrosis in cultured rat thymocytes and S.49 mouse lymphoma and CEM human leukemia cells.

Cell culture systems are widely used to study metabolic changes during apoptosis. In cell culture, unlike in vivo, apoptotic cells are not phagocytosed and eventually lyse (secondary necrosis). This is of practical importance because metabolic changes seen in cultures may be due to the transition from apoptosis to necrosis, rather than to the induction of apoptosis itself. In the present study, we followed the kinetics of the occurrence of several indicators of cell death in rat thymocytes and mouse lymphoma (S.49), and human leukemia (CEM) cell cultures after dexamethasone treatment (10(-6) M). The presence of apoptosis and secondary necrosis was demonstrated by electron microscopy. Nuclear condensation and fragmentation, which are considered to reflect early stages of apoptosis, were visualized with Hoechst fluorescent dye H 33258 for quantitative determination by light microscopy. In S.49 and CEM cultures their incidence increased after glucocorticoid treatment, but remained at relatively low levels not exceeding 6-9% until 36 h (S.49) or 3-4% until 92 h (CEM). The trypan blue positive cells, however, increased steadily to about 60%. Furthermore, flow cytometry (single parameter DNA analysis after propidium iodide staining) revealed the occurrence of cells with reduced DNA fluorescence. Morphological and biochemical (internucleosomal DNA cleavage) analysis of FACS-sorted cells showed that early after dexamethasone the majority of them were apoptotic. In S.49 and CEM cell cultures no clear-cut time lag between increase in cells with reduced DNA fluorescence, chromatin condensation/fragmentation, and the uptake of trypan blue could be detected.(ABSTRACT TRUNCATED AT 250 WORDS)

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