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Biomedical subjects

G M Hahn

Publications and source records attributed to G M Hahn.

At least 145 records · Page 8Linked to original sources
PubMed1977

Cytotoxicity of commonly used solvents at elevated temperatures.

At 43 degrees C (but not at 41 degrees C), organic solvents used to dissolve water-insoluble chemotherapeutic agents become themselves lethal to cells. This finding is not unique to Chinese hamster cells (HA-1); mouse mammary sarcoma cells (EMT-6) behave similarly. The solvent concentrations involved are in the range of those needed to make drug solutions. Hence experiments measuring drug-cell interactions at elevated temperatures must include controls which independently measure solvent effects.

Cell Line↗
PubMed1977

Interaction of amphotericin B and 43 degrees hyperthermia.

At 43 degrees (but not at 41 degrees), the polyene antibiotic amphotericin B effectively inactivates mammalian cells in vitro even at doses which are used prophylactically, routinely, and continuously in some tissue culture laboratories. The greatly enhanced killing may reflect interactions between the drug and hyperthermia at the level of the cells' plasma membrane. A similar enhancement of cell killing at 43 degrees was seen when cells were exposed to nonisotonic salt solutions. Another polyene, nystatin, shows no temperature dependence, at least over the dose range examined, while another antifungal agent, polymyxin B, does so only at very high doses. The in vitro thermosensibility of cells to amphotericin B is reflected in vivo: EMT-6 murine tumor cells were killed much more efficiently in situ at 43 than at 37 degrees. Amphotericin B may be a useful agent in multiple drug thermochemotherapy.

Amphotericin B↗
PubMed1977

Tumor cure and cell survival after localized radiofrequency heating.

Radiofrequency electromagnetic fields at 13.56 MHz were used to heat locally EMT-6 sarcomas and KHJJ carcinomas in BALB/cKa mice. Temperature profiles obtained in tumors during treatment showed uniform temperature distribution throughout the tumor volume with no systemic hyperthermia. Temperature could be maintained at a stable level throughout treatment by adjustment of power. Tumors were treated at 43 degrees, 43-5 degrees, and 44 degrees, for 5, 10, 20, 30, and 40 min. The EMT-6 tumor was highly sensitive to cure by radiofrequency heating: a 5-min exposure at 44 degrees resulted in cure of almost 50% of the tumors. Cure rate was a function of temperature and of duration of exposure. The KHJJ carcinoma was somewhat more resistant to cure by radiofrequency heating, although most of the animals treated at 43.5 degrees or above were cured of their tumors. In an effort to explain the remarkable effectiveness of radiofrequency heating, tumor cell survival studies were done on EMT-6 tumors treated in situ. Cell inactivation by radiofrequency heating was similar to that for hot water bath heating. However, direct cell killing cannot account for the observed cures, and an additional mechanism must be responsible for tumor eradication.

Animals↗
PubMed1976

Cytotoxic effects of hyperthermia and adriamycin on Chinese hamster cells.

Chinese hamster cells, exposed to simultaneous hyperthermia (43 degrees C) and adriamycin (ADM), were intially sensitized to the cytotoxic activity of ADM. If the duration of the combined treatment exceeded about 30 minutes, however, the cells became refractory to additional killing by ADM. If heat was applied before ADM exposure, the cells also could be rendered insensitive; this state persisted so that 24 hours after a 50-minute exposure to 43 degrees C, the cells still showed considerable resistance to ADM. The most reasonable explanation for the findings was that cell membrane permeability to ADM was initially increased by hyperthermia, but prolonged (greater than 30 min) heat exposure reversed this situation and inhibited additional ADM from penetrating to sensitive sites. However, the data yield no hints as to the precise mechanisms involved nor are they sufficiently precise to exclude other explanations. The results do point to precautions that must be observed if the combination of ADM and hyperthermia is to be used clinically.

Cell Membrane Permeability↗
PubMed1976

Recovery of cells from induced, potentially lethal damage.

The recovery of mammalian cells after a variety of treatments is, in part, governed by the cells' ability to deal with repairable, but potentially lethal, lessions. Kinetics of such recovery show a T1/2 of 10-20 hours after ultraviolet (UV) irradiation and 1.5-2.5 hours after X-irradiation. Recovery after exposure to mechlorethamine and bleomycin (BLM) is similar to X-ray recovery; after methylmethane sulfonate, recovery has components similar to X-ray and UV recovery. The sequential treatments of cells with 43 degrees C hyperthermia and X-rays (or reverse order) modify both the immediate survival after treatments as well as the subsequent recovery kinetics. Very similar results are found after BLM and hyperthermia treatments, suggesting strongly that after exposure to that drug a real repair system is operative. However, although recovery after X-irradiation is similar in vitro and in vivo, after BLM the site of treatment and of recovery strongly influences the magnitude and kinetics of recovery.

Bleomycin↗
PubMed1976

Kinetic responses of murine sarcoma cells to radiation and hyperthermia in vivo and in vitro.

Cells of a solid mouse mammary sarcoma that can be cultured in vitro and which, upon inoculation, grow in vivo into new tumors, were exposed either in vivo or in vitro to doses of 300 or 600 rads of X-rays and/or to a temperature of 43 degrees for 1 hr. DNA histograms obtained with flow cytofluorometry were sampled at regular time intervals after treatments in order to obtain information on the cells' postexposure kinetics. X-irradiation of exponentially growing cells induced the expected G2 block; heat exposure caused cells to accumulate in S and G2. The sequential treatment (300 rads followed by 1 hr of hyperthermia) resulted in a mitotic delay that was longer than the sum of the delays of the individual treatments. The proliferative behavior of cycling cells in the tumor treated with a dose of X-rays was qualitatively similar to that seen for exponentially growing cells in vitro; however, marked differences were seen after 43 degrees exposure. The heat treatment of tumors in vivo caused a significant decrease in the tumor cell density as compared to the X-ray treatment alone. Sequential X-ray and heat treatment induced a higher fraction of cycling cells than that found in control tumors. However, X-ray or heat treatment alone caused no significant recruitment of resting cells into cycle 1 day after treatment. A model that permits estimation of the fraction of resting cells in a tumor is described.

Animals↗
PubMed1975

Repair (or recovery) effects in quiescent Chinese hamster cells: an attempt at classification.

Increased survival of density-inhibited Chinese hamster cells after a variety of treatments is analyzed in terms of half-time of "repair," magnitude of repair, and dependence upon nutrient medium during the repair interval. At least three different systems are identified: X-ray-like, UV-like, and an entirely different system after heat shock. Repair after methyl methanesulfonate and after visible light (in bromodeoxyuridine-substituted cells) may be interpreted as a superposition of the X-ray and UV-like repair systems.

Bleomycin↗
PubMed1975

Thermochemotherapy: synergism between hyperthermia (42-43 degrees) and adriamycin (of bleomycin) in mammalian cell inactivation.

The sensitivity of cells exposed in vitro to the antibiotics bleomycin or adriamycin is only mildly increased at 41 degrees over that seen at 37 degrees. However, at 43 degrees a marked synergism between the effects of hyperthermia and drug is observed. This synergism can also be demonstrated to occur in solid tumors in vivo. Cells after bleomycin exposure at 37 degrees repair potentially lethal damage, and 43 degrees inhibits this repair. This inhibition may in part account also for the observed sensitization of the cells to bleomycin, but not to adriamycin, since for the latter no repair can be demonstrated. However, fluorescence measurements show that at 43 degrees much more adriamycin is able to enter the cells than at 37 degrees. The possible implications of the results for cancer treatment are discussed.

Animals↗
PubMed1975

Radiotherapy and chemotherapy: some parallels and differences.

The effects of exposure to ionizing radiations and to various chemotherapeutic agents on the survival of mammalian cells are compared. The relative importance of the cells' sensitivity, age response, proliferative state, and degree of oxygenation and the contributions of kinetic and repair phenomena are examined. Cell killing by high-LET radiations is influenced least by cellular or kinetic factors; thus tumors should show a relatively homogeneous response to this modality, while time-dose relationships should be of least importance. The effectiveness of antimetabolite therapy depends critically on the choice of the correct agents and on tailoring drug administration to the kinetics of both normal and malignant tissue.

Age Factors↗
PubMed1975

Cell cycle progression of murine sarcoma cells after x irradiation or heat shock.

DNA histograms of exponentially growing EMT-6 cells in vitro were obtained at regular time intervals after exposure at 300 rads of x rays or one hour of heat shock at 43 degrees C. After either treatment, about 70% of the cells retained clonogenicity. Irradiation induced the expected block in the G2 + M phase, resulting in an increase of cells in that phase during the first 5 hours after exposure. Heat shock caused a block in both the S and G2 +M phases.

Animals↗
PubMed1975

Enhanced cell killing by bleomycin and 43 degrees hyperthermia and the inhibition of recovery from potentially lethal damage.

The effect of hyperthermia on bleomycin (BLEO) toxicity and repair was studied in "unfed" monolayer cultures of Chinese hamster cells. Synergy of toxicities was observed with simultaneous exposure to BLEO and 43 degrees. For example, when cells were exposed for 1 hr to BLEO (40 mug/ml) at 43 degrees, survival was reduced to 4 X 10(-5); separately, hyperthermia and 37 degrees BLEO exposure each resulted in a survival of 20%. Heating at 43 degrees prior to drug exposure at 37 degrees also produced substantial sensitization, indicating that the primary sensitizing effect involved cell damage rather than an increased rate of drug action; 41 degrees produced only modest cell sensitization to BLEO and the effect was not retained in cells heated prior to drug exposure. No increase in [14C]BLEO uptake was observed at 43 degrees over than at 37 degrees, and thus the increased cytotoxicity was not correlated with a gross change in cell permeability to BLEO, although increased drug availability to particular sensitive targets could not be ruled out. Studies of the repair kinetics after different 43 degrees BLEO protocols demonstrated that most of the cells sustaining potentially lethal damage rapidly recovered. However, 43 degrees hyperthermia inhibited this recovery and, with increasing durations of 43 degrees exposure, the fixation of potentially lethal damage was enhanced. Because of the substantial repair of BLEO damage observed in vivo, the possible usefulness of hyperthermia as an adjunct to BLEO therapy is discussed.

Animals↗