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Biomedical subjects

P S Lin

Publications and source records attributed to P S Lin.

At least 73 records · Page 4Linked to original sources
PubMed1986

Proliferative rates of cloned malignant mammary epithelial cells as a measure of clonal heterogeneity in human breast carcinomas.

Malignant mammary epithelial cells (MMECs) were isolated from 8 human breast carcinomas and 1 adenoma as single cells or organoids and established in vitro. Depending on the cellularity of the tumor, between 9 X 10(4) and 4 X 10(6) cells were released per gram of tumor tissue. With the use of conditioned media and growth-promoting agents, a high proportion of cells (ranging from 0.5 to 11.4%) could be established in culture. A high degree of tumor cell heterogeneity in breast carcinomas was suggested by the observation that significantly different proliferative rates were found for 50 mammary epithelial cells cloned from 2 different tumors during the first subpassage in vitro prior to significant expansion of the cell colonies. The computed doubling times of these clones varied between 16 hours and more than 48 hours. The mammary epithelial nature of the cells was confirmed by their surface reactivity with monoclonal antibodies specific for MMECs. Studies on clones from 2 tumors revealed a positive correlation between proliferative rates of MMECs, their lactate production, and specific proteins synthesized as analyzed by two-dimensional macromolecular protein maps.

Antibodies, Monoclonal↗
PubMed1985

Peak temperature influences on heating rate effect in hyperthermic cytotoxicity.

Exponentially growing Chinese hamster V79 cells were heated from 37 degrees C up to 42 degrees C or 43 degrees C at four different heating rates: immediate exposure, 1/2 hour, 1 hour, and 2 hours. The D0's of the heat survival curves for both 42 degrees C and 43 degrees C were determined for the different heating rates. The results show that the decrease in toxicity to cells at 43 degrees C resulting from a slower heating rate appears to be less pronounced than that at 42 degrees C. However, the thermotolerance ratio is found to depend on the specific heating time (the reciprocal of the heating rate), in a linear fashion and it does not seem to depend on the peak temperature. We propose that the difference in the heat exchange on cell membranes at different rates of heating may contribute to the causes for the difference in cell sensitivity to hyperthermia.

Animals↗
PubMed1985

The diethyldithiocarbamate concentration effects and interactions with other cytotoxic agents on Chinese Hamster cells (V79).

A metal chelator, diethyldithiocarbamate (DDC) perturbs the chromosome condensation processes in dividing cells. The length of the metaphase chromosomes in Chinese hamster cells (V79) treated with 17.2 micrograms/ml of DDC for 2 hr is about half of that in untreated cells. However, concentrations of 1.7 microgram or 172 micrograms/ml DDC apparently do not produce this effect. DDC at 17.2 micrograms/ml also disrupts spindle fibers. Penicillamine, EDTA, EGTA, and diamide show no effect on chromosome condensation. Bleomycin, but not mitomycin and cisplatin, added simultaneously with DDC can prevent the DDC effect on chromosomes. The cytotoxic effect of increasing concentrations of DDC to V79 cells incubated at 37 degrees C exhibits a similar biphasic response. This concentration biphasic toxic effect is not altered when the cells are treated with DDC in combination with radiation, heat, or other cytotoxic drugs. These observations suggest that the different effects of DDC concentrations on chromosome condensation should be considered as one important modification factor for DDC related toxicity.

Animals↗
PubMed1985

A comparison of the effects of hyperthermia on cell growth in human T and B lymphoid cells: relationship to alterations in plasma membrane transport properties.

Hyperthermic exposure (39-43 degrees C) for 1 or 2 hr impairs growth and Na+-dependent amino acid transport in both a radiosensitive human T (Molt-4) and a radioresistant B (RPMI 1788) lymphoid cell line. The heat damage to Na+-dependent amino acid transport in both cell lines is reversible under the conditions tested. Cell growth, as judged by increases in cell number, is decreased in both cell lines after hyperthermic treatment (43 degrees C, 1-hr exposure). This decrease in growth correlated with the damage to, and recovery of, the Na+-dependent amino acid transport system. However, the sensitivity to heat of both growth and Na+-dependent amino acid transport appears to differ in Molt-4 which is somewhat more sensitive to hyperthermia (T-cell line) vs RPMI-1788 (B-cell line). In the case of Molt-4, the rate of growth is decreased for about 60-80 hr after cells are exposed for 1 hr at 43 degrees C; whereas increases in cell number in the RPMI 1788 is observed within 40 hr after the heat treatment. The differences observed in cell growth and transport in these two lymphoid cell lines are attributed to the manner in which heat affects (i) the transport parameters in Molt-4 vs RPMI 1788 (i.e., the Michaelis-Menten constants Km and Vmax) and (ii) the putative plasma membrane sulfhydryl protein(s) which modulates Na+-dependent amino acid transport.

Aminoisobutyric Acids↗
PubMed1984

Modification of membrane function, protein synthesis, and heat killing effect in cultured Chinese hamster cells by glycerol and D2O1.

Glycerol and D2O can provide a protective effect to Chinese hamster V79 cells receiving heat treatment. The mechanism for this effect is assumed to be the ability of these agents to stabilize proteins which implies that one of the possible heat-killing mechanisms is the inactivation of a heat-sensitive molecule (protein?). In addition, we observed that heat can alter the membrane permeability rapidly, and glycerol can reduce the initial heat-induced membrane permeability changes (determined by aminoisobutyric acid uptake). Although not as effective as cycloheximide, glycerol and D2O can retard protein synthesis. These two processes can add to the protective effect of stabilizing cellular protein against heat killing. Since glycerol and D2O added during the heat-conditioning period can interfere with the appearance of thermotolerance, the mechanisms for the protective effect of glycerol and D2O are likely to be different from heat-induced thermotolerance. We propose that the heat-sensitive molecule protected by D2O or glycerol may also play a role in the triggering process of the thermotolerance phenomenon. If the conditioning heat treatment is sufficient to affect this molecule but not other cellular targets, thus allowing the cell to survive, thermotolerance may be observed in surviving cells in response to second or continued heat treatment. Depending on the severity of the heat effect, this heat-sensitive molecule may continue to exist after a conditioning heat treatment in medium containing glycerol or D2O, and therefore, the response of the cells to the challenging heat is altered little. This proposed mechanism is capable of explaining several thermotolerance experimental protocols. Since glycerol can also reduce the toxicity of vincristine, microtubule-related protein is probably one of the proteins stabilized by this agent. D2O also probably affects microtubule protein, because the cells heated in medium containing D2O show little topological changes.

Aminoisobutyric Acids↗
PubMed1983

Ultrastructural changes of bovine pulmonary artery endothelial cells irradiated in vitro with a 137Cs source.

Bovine pulmonary artery endothelial cells in culture were evaluated by phase-contrast and electron microscopy at various times after being irradiated with 137Cs in vitro. Cells irradiated prior to reaching confluency showed vacuolization aand increased numbers of lysosomes beginning at 48 hr after irradiation with 300-500 rad and at 24 hr after irradiation with 1500-5000 rad. After 7 days the morphological changes appeared to be reversible for cells receiving the lower doses, but were progressive for higher doses of radiation. The same qualitative changes, with a delayed onset, were observed for cells irradiated at confluency. An observed decrease in the endoplasmic reticulum and polysomes occurred only late in the course of radiation injury. There was no observable structural alteration of mitochondria even when there was evidence of otherwise marked cytoplasmic injury. We conclude that structural changes of the lysosomes constitute an early phase of injury by irradiation of the endothelial cell in culture, while decreases in endoplasmic reticulum and polysomes occur relatively late. The mitochondrial structure of the endothelial cell appears to be relatively resistant to radiation. All morphological changes occur subsequent to impaired transport of alpha-aminoisobutyric acid, which is observed within 6 hr as previously reported.

Animals↗
PubMed1983

Work in progress: the effect of heat on bleomycin cytotoxicity in vitro and on the accumulation of 57Co-bleomycin in heat-treated rat tumors.

The cytotoxic effects of the sequence and timing in combined hyperthermia and bleomycin treatment were tested in vitro using V79 Chinese hamster cells. The order of treatment was important; heat treatment followed by the administration of bleomycin yielded greater cytotoxicity than when the opposite order was used. To determine whether heat-treated tumors have an altered uptake of bleomycin, rat rhabdomyosarcoma (BA 1112) tumors were heated locally with RF current (43 degrees C, 90 min.), injected with 57Co-bleomycin, and imaged on a radioisotope camera. Results of tumor-to-background (T/B) ratio analysis indicate that (a) local hyperthermia (43 degrees C) does not appear to alter tumor uptake patterns of 57Co-bleomycin; and (b) intravenous and intraperitoneal injections produce similar T/B uptake ratios, typically between 2 and 3 at 120 minutes postinjection. In the BA 1112/WAG/Rij tumor system, local hyperthermia treatment does not seem to interfere with the subsequent accumulation of bleomycin in the tumor.

Animals↗
PubMed1983

Effects of iron, copper, cobalt, and their chelators on the cytotoxicity of bleomycin.

Bleomycin is widely used for treating several types of human tumors as well as a variety of experimental tumors. The ability of this antibiotic to bind and to damage DNA has been proposed to be responsible for its antitumor effect. Bleomycin is also a good chelator for several metals, e.g., iron, copper, and others. Bleomycin:metal complexes have been investigated in detail particularly for their action on isolated DNA. The conclusions from these studies indicate that metal-chelated bleomycin either is ineffective or more effective in damaging DNA. In this paper, we tested the effect of iron, copper, cobalt, and their chelators on bleomycin cytotoxicity. Our results suggest that chelating bleomycin with copper or adding an iron chelator (deferoxamine), diethylenetriamine pentaacetic acid, and a copper chelator (penicillamine) shows no effect on bleomycin cytotoxicity. On the other hand, iron dextran and a metal chelator, diethyldithiocarbamate (DDC), with bleomycin show enhanced cytotoxicity. Cobalt-chelated bleomycin is not cytotoxic but is cytotoxic when combined with DDC. We suggest that different mechanisms are contributing to the enhanced toxicity of bleomycin with iron dextran and DDC. Bleomycin acts as a ferrous oxidase which promotes the iron toxicity. In the case of DDC, it can act as a reducing agent or it can help to maintain the bleomycin:metal complex in the reduced form which can generate radicals.

Animals↗
PubMed1983

Hyperthermia and bleomycin schedules on V79 Chinese hamster cell cytotoxicity in vitro.

The effect of sequence and timing of hyperthermia (43 degrees) and bleomycin on Chinese hamster cells (V79) has been investigated. Hyperthermia preceding bleomycin treatment produced a greater cytotoxic effect than bleomycin treatment preceding hyperthermia. Furthermore, it appears that the combination of hyperthermia and bleomycin becomes less effective if the application of bleomycin is delayed. The enhancement of cytotoxicity with hyperthermia first may be related to the effect of heat on the intracellular bleomycin degradation ability and protein synthesis. V79 cells treated with a protein synthesis inhibitor, cycloheximide, before bleomycin (but not in the reversed sequence) also showed a markedly lower level of survival. As for hyperthermia treatment, pretreatment with cycloheximide did not change the uptake of bleomycin. These results suggest that hyperthermia and cycloheximide have increased the effectiveness of bleomycin and are consistent with the observation on chromosome damage induced by hyperthermia-bleomycin and cycloheximide-bleomycin treatments reported in the literature.

Animals↗
PubMed1982

Endothelial cell damage after gamma-irradiation in vitro: impaired uptake of alpha-aminoisobutyric acid.

The effects of gamma-irradiation with a cesium-137 source were assessed on endothelial cells isolated from bovine pulmonary arteries and maintained in culture. The radiobiologic parameters that characterize the dose-response survival curve for these cells, expressed as mean +/- SD were found to be n = 1.6 +/- 0.2, Dq = 71 +/- 13 rads, and Do = 161 +/- 35 rads, indicating a relatively low capacity of these cells to accumulate or repair radiation damage. Increasing doses of radiation led to decreasing uptake by endothelial cells of [14C]2-aminoisobutyric acid (AIB), a Na+-dependent and nonmetabolizable amino acid. A dose of 500 rads, which caused marked inhibition of cell survival, resulted in a 45% decrease in AIB uptake at 6 h and a 69% decrease in uptake at 24 h after irradiation. No morphologic abnormality was noted in these cells by light microscopy at 24 h after this dose of radiation. Bovine pulmonary artery fibroblasts, on the other hand, showed no significant impairment in uptake of AIB 24 h after exposure to doses of radiation as high as 5,000 rads. The uptake by endothelial cells of [14C]1-aminocyclopentane-1-carboxylic acid, an amino acid transported by a Na+-independent process, was not influenced by 5,000 rads of radiation. Our studies show that endothelial cells are sensitive to radiation and that impaired Na+-dependent uptake of AIB represents an early event in radiation damage to the endothelial cell.

Aminoisobutyric Acids↗
PubMed1981

Protection of heat induced cytoxicity by glycerol.

Glycerol, at concentrations of 2-10% is a potent hyperthermic (43 degrees - 45 degrees C)protector of cultured Chinese hamster cells, V79. Furthermore, the sensitization effect of low pH on heat death is also drastically reduced by the addition of glycerol into the culture medium. Together with the known cellular effects of heat and the role of glycerol in various cellular structures and functions, the data suggest that microtubules and membranes may be involved in the expression of heat-induced cell death.

Animals↗
PubMed1981

The efficacy of several irrigating solutions for endodontics: a scanning electron microscopic study.

The perforated irrigation needle was used to test a high-volume (20 c.c.) final flush of prepared root canals. Three solutions: TEGO 1 percent, NaOCl 5.25 percent, and REDTA were tested. The roots were split longitudinally and were prepared for examination under the scanning electron microscope immediately after preparation and final flushing. In addition, groups were prepared and flushed in the same manner, but after splitting they were soaked in the respective solutions for 3 hours and then examined. The results indicated that the smeared layer is caused by instrumentation, that it is not removed by TEGO or NaOCl, and that it is removed by REDTA. It may be that the smeared layer is a slurry of dentin filings, since REDTA does not remove soft tissue. All solutions produced a canal quite free of debris; however, none of the tested irrigants was completely satisfactory by itself.

Dentin↗
PubMed1981

Electron microscopic study of hemolysis: a proposal of formation of a weak structural region in the erythrocyte membrane.

Numerous theories have been advanced to explain the erythrocyte shape in terms of membrane structure. One of the most controversial points has been whether the erythrocyte membrane is a uniform shell. Electron microscopy studies of erythrocytes undergoing osmotic lysis show that the release of hemoglobin is confined to one large area, suggesting that this area is more fragile structurally than that of the rest of the surface membrane. Hypotheses are presented to explain the formation of structurally weak areas on the erythrocyte membrane.

Biophysical Phenomena↗
PubMed1981

Effect of the superoxide anion (O2-) on Na+-dependent amino acid transport.

Superoxide anion (O2-) generated either by the autoxidation of dihydroxyfumaric acid (DHF) or enzymatically by the xanthine-xanthine oxidase system inhibited the uptake of 2-aminoisobutyric acid (AIB) in thymocytes. The transport of this non-metabolizable amino acid in thymocytes is mediated by a Na+-dependent mechanism. Inhibition of this transport system by O2- was similar to that observed when radiosensitive lymphocytes are subjected to ionizing radiation. As in irradiated thymocytes, O2- generation affected primarily the maximal rate of uptake of the amino acid (i.e. Vmax). No change was observed in the apparent affinity of the amino acid for its carrier (i.e. Km) or the efflux rate of the amino acid. The data suggests that the superoxide anion may be one of the major species responsible for the observed radiation damage to radiosensitive lymphoid cells.

Aminoisobutyric Acids↗