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S Rockwell

Publications and source records attributed to S Rockwell.

At least 145 records · Page 8Linked to original sources
PubMed1981

A mathematical model for analysing cellular age-response functions in terms of physiological age.

A mathematical model is presented which facilitates the analysis of cellular age-response functions in terms of the physiological ages of the cells. Age-response functions are generally determined by obtaining synchronous cohorts of cells and measuring the sensitivity of the cohorts to the treatment agent at different times after selection (i.e., several different chronological ages). The model described here uses data on the [3H]TdR labelling patterns of the cell population to determine the distribution of physiological ages for the cohorts at the times of treatment. The age-response function data are then analysed in terms of the physiological ages of the cells. The compartments used in the analysis may be chosen according to the biology of the system and the wishes of the experimenters and not imposed by the variability of the phase durations. The application of the model is illustrated using the age-response functions for EMT6 cells exposed to radiation and HeLa cells exposed to hydroxyurea.

Animals↗
PubMed1981

Effect of host age on the transplantation, growth, and radiation response of EMT6 tumors.

The characteristics of EMT6 tumors in young adult (3- to 4-month-old) and aged (20- to 28-month-old) BALB/c KaRw mice were compared. The number of tumor cells implanted s.c. necessary to cause tumors in 50% of the injection sites was lower in aging than in young adult mice (69 and 138 cells for young adult mice versus 8.8 and 16 cells for aging mice in two experiments). The latent period of intradermally implanted tumors was shorter in aging mice than in young animals; however, the growth curves of established tumors were similar. The number and appearance of lung colonies after injection of cells i.v. and the pattern of spontaneous metastases were similar in young and aged animals. The cloning efficiencies (viabilities) of cells suspended from tumors in young adult and aging animals were the same (approximately 30% in both groups). Radiation dose-response curves for the cells of tumors in young and aging mice were different and suggested that the proportion of hypoxic cells was higher in tumors on aging animals. These findings suggest that both immunological and nonimmunological tumor-host interactions differ in young and aged animals and that such factors may influence the natural history of the tumor and the response of the tumor to treatment.

Aging↗
PubMed1980

Cell proliferation in EMT6 tumours treated with single doses of X-rays or hydroxyurea. II. Computer simulations.

A computer simulation technique was used to analyse data on the proliferation of clonogenic cells in EMT6 tumours treated with 5 mg/mouse of hydroxyurea (HU) or 3.0 Gy (300 rads) X-rays. This simulation technique is able to determine the respective roles of selective killing, blocks in cell progression and recruitment of the treated population. When the technique was applied to tumours treated with HU, it was possible to prove that both a G1/S block and recruitment occurred. These phenomena could not have been demonstrated quantitatively, or even qualitatively, without the use of the simulation. After irradiation, blocks in cell progression and differences in the proliferative patterns of the surviving clonogenic cells and the total tumour cell population were found.

Animals↗
PubMed1980

In vivo-in vitro tumour cell lines: characteristics and limitations as models for human cancer.

In vivo-in vitro tumour cell lines are widely used to study the biology of cancer and to examine the factors influencing the response of tumours to therapeutic agents and regimens. The existing in vivo-in vitro tumours form a uniform and artificial population of experimental neoplasms, with biological characteristics which limit the acceptability of any of these tumours or panel of these tumours as an accurate model for human cancer. All are rapidly growing, transplanted tumours in highly inbred rodents. All have growth rates, cell proliferation patterns and tumour-host interactions different from those of primary tumours in animals or man. Most are immunogenic. Most are anaplastic sarcomas: few are carcinomas; none are well differentiated. The biological differences between in vivo-in vitro tumours and human neoplasms must be considered when the experimental systems are used as models for human cancer.

Animals↗
PubMed1980

Preferential activation of mitomycin C to cytotoxic metabolites by hypoxic tumor cells.

Mitomycin C, a bioreductive alkylating agent with clinical utility against several human tumors, was found to be selectively toxic at a relatively low concentration (1.5 micro M) to EMT6 tumor cells made chronically hypoxic by preincubation in 95% N2-5% CO2 for 4 hr prior to drug exposure. This selective cytotoxicity correlated well with the preferential activation and metabolism of mitomycin C by sonicated cell preparations. The bioactivation of mitomycin C to an alkylating agent by EMT6 and Sarcoma 180 cell sonicates required hypoxic conditions and a reduced nicotinamide adenine dinucleotide phosphate-generating system. Furthermore, the formation of reactive drug metabolites and the disappearance of mitomycin C from the reaction mixture were inhibited by carbon monoxide. The presence of potassium cyanide in the incubation mixture did not affect either the rate of overall metabolism or the rate of formation of reactive metabolites. A high rate of disappearance of mitomycin C from the medium of intact cultures of EMT6 cells was found only in those cultures which were made chronically hypoxic. These data suggest that bioreductive alkylating agents like mitomycin C have the potential to attack selectively the chemotherapeutically resistant hypoxic cell component of solid tumors. Thus, agents capable of bioreductive alkylation should be useful adjuncts to existing therapeutic regimens which are effective against well-oxygenated cells.

Alkylating Agents↗
PubMed1978

Cell proliferation in EMT6 tumors treated with single doses of x-rays or hydroxyurea. I. Experimental results.

EMT6 mouse mammary tumors were treated in vivo with 5 mg/mouse of hydroxyurea (HU) or 300 rads of X-rays. The proliferation of the tumor cells was followed for 28 hr after treatment. Changes in the 3H-TdR labeling index, the mitotic index, the specific activity of the 3H-TdR-labeled DNA, and the proportion of suspended, clonogenic cells in the S phase of the cell cycle were examined and compared. Evidence was found for reassortment of the surviving cells in treated tumors into partially synchronous cohorts. The partial synchrony in the proliferation of the surviving cells was not accurately predicted by the changes in the labeling index and the mitotic index. The changes in DNA specific activity proved unacceptable as an indicator of cell proliferation in solid EMT6 tumors treated with low doses of radiation or HU.

Animals↗
PubMed1978

Cytotoxic and radiosensitizing effects of hypoxic cell sensitizers on EMT6 mouse mammary tumour cells in vivo and in vitro.

The radiosensitizing activities and toxicities of misonidazole, metronidazole, 2-Methythio-3-nitropyrrole (3NPR), 2-amino-5-nitrothiazole (ANT) and 2,5-dinitroimidazole (KA121) were studied using EMT6 tumour cells and BALB/c KaRw mice. For 10(-4)M concentrations of the drugs, the DMF's for hypoxic cells were: Misonidazole, 1.6; 3NPR, 1.5, ANT, 1.5; KA121, 1.8. The OER was 3.2. In general, the drugs were toxic to hypoxic cells and were not toxic to aerobic cells at 10(-3)M for 24 h. The LD50's in BALB/c KaRw mice were: misonidazole, 1500 mg/kg; 3NPR, 350 mg/kg ANT, 420 mg/kg. In vivo, 1 mg/g misonidazole or metronidazole reduced the terminal slope of the tumour cell survival curve by a factor of 2.2 or 1.6 respectively.

Animals↗
PubMed1977

Influence of a 1400-gauss magnetic field on the radiosensitivity and recovery of EMT6 cells in vitro.

EMT6 mouse mammary tumour cells in vitro were exposed to an almost uniform 1400-gauss magnetic field during or after irradiation with 120 kV X-rays. Exposure of unirradiated control cultures to this field for up to 48 hours did not alter the viability or growth of the cells. Exposure of exponentially-growing cultures to the magnetic field during irradiation did not alter the survival curve. Exposure of exponentially-growing culturesto the magnetic field between two doses of 500 rad of X-rays did not alter significantly the pattern or magnitude of the recovery from sub-lethal damage. Exposure of plateau phase cultures to the magnetic field after irradiation did not alter significantly the pattern or magnitude of recovery from potentially-lethal damage. The effects of a short exposure to an almost uniform magnetic field of this strength on the production and repair of radiation damage appear to be minimal in this system.

Cell Line↗
PubMed1976

A technique for determining the proportion of the clonogenic cells in S phase in ENT6 cell cultures and tumors.

The survival of cultured EMT6 cells was examined after treatment with hydroxyurea (HU) or high specific activity tritiated thymidine (3H-TdR). The concentrations of the agents, duration of exposure to the agents, and post-exposure treatment of the cultures were found to influence the cell survival; the effects of these factors are reported. Conditions were defined under which the proportions of cells killed by HU and by 3H-TdR were the same and were also the same as the proportion of labeled cells seen on autoradiographs of cultures labeled with small doses of 3H-TdR. Under these conditions, either 3H-TdR or HU could be used to determine the proportion of the clonogenic cells in S phase. Single cell suspensions prepared from solid EMT6 tumors were treated in vitro with HU or 3H-TdR, using the conditions found optimal for each agent with cultured cells. The proportion of the tumor cells killed by treatment with HU in vitro was the same as the proportion killed by HU in vivo and as the proportion labeled by 3H-TdR in vivo, and incubation of tumor cell suspensions with HU in vitro appeared to provide a valid measurement of the proportion of clonogeneic tumor cells in S phase. Incubation of tumor cell suspensions with 3H-TdR in vitro proved difficult to perform and the results were relatively unreliable because of severe problems with reutilization of 3H-TdR during the incubation for colony formation.

Animals↗