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H M Rabes

Publications and source records attributed to H M Rabes.

At least 73 records · Page 4Linked to original sources
PubMed1983

DNA alkylation and tumor induction in regenerating rat liver after cell cycle-related continuous N-nitrosodimethylamine infusion.

Synchronized regenerating rat liver after partial hepatectomy was used to study cell cycle-related DNA base alkylation and liver carcinogenesis. A continuous iv infusion of [14C]N-nitrosodimethylamine (DMN) at a dose of 0.5 mg/kg/hour was given to inbred male Wistar Af/Han rats over a period of 8 hours either during the G1 phase, hydroxyurea-synchronized DNA synthesis, or the G2+M-phase of regenerating liver or to untreated rats (G0-phase liver--carcinogen dose, 1.5 mg/kg/hour). Two hours after the end of the infusion, the amount of 7-methylguanine was highest in the G0-phase liver, with a decrease in the G1 phase, the S-phase, and the G2+M-phase. After continuous DMN exposure, the O6-methylguanine:7-methylguanine ratio was lower in the S-phase and G2+M-phase livers than in the G0-phase and G1-phase livers, indicating an increased O6-methylguanine repair during DNA synthesis and the G2+M-phase. Liver tumors in rats treated by continuous DMN infusion either during the G0 phase or the S-phase developed only after carcinogen exposure during DNA synthesis.

Adenine↗
PubMed1979

Analysis of proliferative compartments in human tumors. I. Renal adenocarcinoma.

Vascular perfusion of 16 renal adenocarcinomas with radioactive DNA precursors provides a possibility of characterize proliferative compartments of this tumor type. Immediately after resection of the tumor-bearing kidney, the organ is perfused via renal artery with dextran-diluted, heparinized oxygenated blood at physiological temperature, pH, flow, and pressure in a recirculation system. DNA synthetizing cells are labeled by addition of 3H- or 14C-thymidine or both isotopes at different intervals. Beta camera scans and whole-tumor autoradiograms disclose a striking proliferative heterogeneity of the tumor. Cell proliferation depends on intratumoral localization, cellular differentiation, histological structure and vascular supply. Subpopulations of high proliferative activity are found at the invasive borderline near normal kidney, focally in subcapsular areas and in intrarenal metastases, but also immediately adjacent to necrotic areas in the tumor center. Quantitative evaluation of autoradiograms yields, at the cellular level, a significantly higher labeling index in granular cells (3.21%) than in clear cells (0.65%), with a large variability dependent on the histological structure. The highest number of DNA synthetizing cells is seen in papillary and mixed solid-tubular zones and at peripheral parts of solid areas, whereas in central parts of solid tumor cords and in highly differentiated tubular areas lower labeling indices are observed. The labeling index decreases exponentially as a function of the distance from the supporting blood vessel. In solid cords, no labeled cells are seen at a distance of more than 200 micron from the capillary. The ts determined by 3H/14C-thymidine double labeling is between 9.9 and 16.8 hr for granular cells and about 9.2 hr for clear cells. Potential population doubling time calculated for various subpopulations yields values between 4 and 50 days. It is concluded that cell loss is high, for granular cells in particular. Besides cell loss, a large nonproliferating compartment contributes to a delay of the tumor volume doubling time. Proliferative heterogeneity of advanced human tumors, as exemplified by the renal adenocarcinoma, bears important implications for therapy and prognosis.

Adenocarcinoma↗
PubMed1977

Kinetics of hepatocellular proliferation as a function of the microvascular structure and functional state of the liver.

An analysis of hepatocellular proliferation in regenerating rat liver reveals a dependence of kinetic parameters on the microvascular structure of the liver. Influx kinetics of hepatocytes into DNA synthesis as well as cell cycle phases vary in different parts of the liver lobule between the afferent and efferent vascular poles. Heterogeneity of the proliferative response and size limitations on cell cycle compartments appear to be intimately related to the actual functional state of the individual liver cell. Modifications of liver cell functions result in variations of the proliferative activity. Phenobarbital-induced hypertrophy of hepatocytes reveals a permissive action on G1- S influx. Selective destruction of the subpopulations, by allyl formate, leads to a new functional determination of the residual liver and to a change in proliferative compartments. Maximum modulation of cell cycle compartments is obtained by hydroxyurea-induced synchronization of hepatocytes after partial liver resection. During hydroxyurea treatment, the regenerating liver shows a pronounced cellular hypertrophy. After release from hydroxyurea block, cells embark on DNA synthesis simultaneously. The DNA synthesizing compartment comprises almost the entire liver cell population. Heptotrophic factors might play a part in regulating or modifying hepatocellular function and proliferative response after cell loss.

Allyl Compounds↗
PubMed1977

Grain count threshold dependence of FLM curve pattern and cell cycle parameters of hepatocytes in vivo.

FLM curves from hepatocytes of regenerating rat liver in vivo were compared at different grain count thresholds. Estimates of cell cycle phases derived from curves with thresholds decreasing from 15 to 1 grain (background 0-2 grains per nuclear area) revealed a prolongation of ts from 6-6 to 9-5 hr, at the expense of tG2M, and tG1, whereas tc remained constant. A similar pattern was observed in FLM curves at various threshold levels for hepatocytes localized in subunits of the liver lobule along the vascular axis from afferent to efferent pole. The shapes of these FLM curves indicated an intralobular gradient of reutilizable labelled material. The use of two different threshold levels is crucial for proper selection of FLM curves to evaluate cell cycle phases in regenerating rat liver: first, threshold to exclude the autoradiographic background, and a second one to avoid errors due to reutilization of labelled DNA precursors. Each threshold has its own implications for the estimation of cell cycle phases.

Animals↗
PubMed1977

Synchronization of hepatocellular DNA synthesis in regenerating rat liver by continuous infusion of hydroxyurea.

Hydroxyurea (HU) inhibited DNA synthesis in the livers of partially hepatectomized rats. After an i.v. infusion of HU begun in the late G1 phase and continued for periods of up to 30 hr, all hepatocytes scheduled to embark on DNA synthesis in a characteristic intralobular sequence during this time interval accumulated at the G1-S boundary. The effective dose was 1.25 mmoles/kg/hr, preceded by a single injection of 1.69 mmoles/kg. Serum levels of HU rose slightly during continuous infusion and decreased after termination, with a half-life of about 80 min. Liver weight increased during HU infusion. The G1-S blockade was rapidly reversed in the liver after the end of HU infusion. The specific activity of DNA increased to a maximum between 3 and 5 hr. [3H]Thymidine labeling indices reached about 80%. Intralobular distribution of labeled hepatocytes was congruent to the pattern seen in partially hepatectomized rats after a continuous [3H]thymidine infusion of equal duration. The beginning of DNA synthesis in nonparenchymal cells was delayed, as compared with hepatocytes. Vincristine infusion for 12 hr after release from the HU block arrested about 40% of the hepatocytes in mitosis, indicating that a large fraction of cells progressed through the cycle after the prolonged HU block. Partially resected rat liver appeared to be rather resistant to the unfavorable consequences of "unbalanced growth" during the protracted inhibition of DNA synthesis, providing a useful model for synchronization of DNA synthesis in a differentiated resting organ triggered into active growth.

Animals↗
PubMed1976

Analysis of cell cycle compartments of hepatocytes after partial hepatecomy.

An analysis of cell kinetic parameters as a function of intralobular localization of hepatocytes was performed using autoradiographic methods to obtain a basis for a quantitative description of cell cycle compartments after partial hepatectomy. The influx into the S compartment revealed a maximum in a lobular zone not immediately adjacent to the portal tract, with a decrease towards the perivenous and periportal area of the lobule. The maximum influx was found in the intermediate zone at 34 hr and a lower one in the perivenous parts of the lobule at 40 hr. The influx pattern at 56 hr was similar to the situation at 18 hr. The fraction of labelled mitoses in the whole liver and in subunits of the lobule disclosed a constant duration of S whereas the duration of G2 + M was prolonged from the periportal to the perivenous zone. A graphical model of kinetic events after partial hepatectomy is proposed, which describes the sizes of the various cell cycle compartments; the model successfully predicted the results of a continuous labelling experiment.

Animals↗
PubMed1975

[Cell kinetic studies on the interference between proliferative and functional metabolism in regenerating rat liver after application of phenobarbital (author's transl)].

To investigate the correlation between fuction and proliferation, cell kinetic studies were carried out in regenerating liver of phenobarbital (PB) treated rats. Male adult Wistar rats received i.p. injections of 90 mgPB/kg body weight daily for five days (group A). Rats of group B received additional injections of PB at a reduced dose (30mg/kg) every 12 hrs after partial hepatectomy, starting immediately after the operation. 60 min after a single injection of 3-H-TdR at different intervals after surgery, specific activity of DNA, 3=H=TdR labeling index, and mitotic index were determined. Intralobular distribution of DNA-synthesizing hepatocytes was analyzed in 22 h regenerating liver. Stimulation of fuctional activities by PB results in a transitional synchronization of the start of DNA synthesis in liver parenchymal cells after partial hepatectomy. The labeling indices of group A and B increase to 36% and 30%, respectistribution of DNA-synthesizing hepatocytes revealed that higher levels of synchronization are limited to periportal zones of the liver lobule which provide optimal conditions of G1-S transition. PB treatment apparently does not influence duration of S,G2 or M under these conditions. The results stress the possibility that transitional synchronization of DNA synthesis by functional load might simulate stimulation of growth in a proliferating population.

Animals↗