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L J Tolmach

Publications and source records attributed to L J Tolmach.

At least 37 records · Page 2Linked to original sources
PubMed1977

Cellular inactivation by ultrasound.

The lethal effect of ultrasound (US) on mammalian cells has received relatively little attention. Understandably, potential genetic aspects of US have been of prime concern to physicians who use US as a diagnostic tool; at the average power densities involved (<<1 W cm(-2)) little, if any cell killing is to be expected. There have been sporadic attempts to use higher intensities ( approximately 1 W cm(-2)) as a treatment modality in cancer therapy, but those experiments seem to have been based on inadequate cellular studies. The effects of US usually were evaluated in terms of morphological criteria rather than on quantitative determination of the loss of viability as measured by colony formation. There are few reports of the effects of US on survival of mammalian cells, and none specifically examine hyperthermic interaction. With the increased interest in hyperthermia for tumour therapy, attention has been directed towards the use of ultrasound to achieve tumour heating. In preliminary experiments in which US was used to heat the EMT6 sarcoma and KHJJ carcinoma in mice, we found a high percentage of tumour cures with short (approximately 30 min) treatments at temperatures (43-44 degrees C) where in vitro results of hyperthermia-induced cell killing would not have led to a prediction of any cures. We therefore initiated an investigation of the effects of US on survival of Chinese hamster cells to see if direct cell killing by US could explain our in vivo results, or, as in the case of radiofrequency (RF) electromagnetic heating, we would be forced to invoke host response(8). In particular, we examined the thermal and non-thermal components of cellular inactivation by US. We report here that there is a definite non-thermal cytotoxic effect of US. Its relative contribution to cell killing is a highly nonlinear function of the temperature of the cellular milieu. The survival curves show clearly that, beyond an initial threshold, small changes in temperature and/or US intensity can give rise to impressive changes in survival values. The threshold nature of the data strongly suggests that by means of overlapping beams, ultrasound energy could be delivered to tumour tissue to achieve massive cell killings while sparing normal tissue outside the tumour volume to a degree far exceeding that of conventional techniques.

Animals↗
PubMed1976

Lethal response of HeLa cells to x-irradiation in the latter part of the generation cycle.

The age-response for the killing of HeLa S3 cells by X-rays during the latter part of the generation cycle has been examined in detail. As synchronous cells move from the G1/S boundary through S phase, the relatively high sensitivity of late G1 cells gradually decreases; minimum sensitivity is reached in mid-S and maintained during the remainder of that phase. The response of cells as they progress from S to the point in G2 at which they are temporarily arrested by radiation (or by inhibitors of protein synthesis) was measured in populations free of both S phase cells and late G2 cells that had passed the arrest point: cells retain their high resistance from early G2 up to the arrest point. The response of G2 cells that have passed the arrest point before being irradiated was examined by exposing randomly growing cultures to X-rays and collecting cells periodically thereafter, as they entered mitosis. Survival values very close to those of sensitive mitotic cells were found in the 2 h period after irradiation during which unarrested cells continued to reach mitosis. Values typical of lateS/early G2 were found only after cells that had been arrested began arriving at mitosis. Thus, HeLa S3 cell undergo an abrupt increase in sensitivity at or near the arrest point. The sensitivity to a second irradiation of cells arrested in G2 by a conditioning X-ray dose increases rapidly in the early part of the arrest period.

Cell Survival↗
PubMed1969

Time lapse cinemicrographic studies of x-irradiated HeLa S3 cells. I. Cell progression and cell disintegration.

Time-lapse cinemicrographs of synchronous HeLa S3 cells irradiated with 220 kv X-rays at various stages of interphase provided data for constructing pedigrees, measuring the duration of both generation cycles and mitoses, and scoring events associated with cell disintegration for up to seven postirradiation generations. The onset of the first mitosis after doses of 500 rads was delayed as expected from previous studies of the age dependence of "mitotic delay." The interval between this first mitosis and the next was indistinguishable from that for unirradiated control cells, while the subsequent two generations were again prolonged, on the average, though not so severely as was the irradiated generation. The duration of mitosis was increased proportionally more than interphase. Cell disintegration took place by way of two morphologically distinct processes. In three-quarters of the cases the cells were rounded and apparently trapped in metaphase when they disintegrated; the remaining disintegrations occurred in spread, interphase cells. In cells disintegrating from the rounded configuration, the generation preceding disintegration was prolonged relative to that in cells which divided; in cells disintegrating from either configuration, the penultimate generation was also prolonged. The mitotic times were disproportionately increased in both of these generations. It is suggested that in this system X-ray damage is preferentially expressed as derangement of the mitotic process; such damage ultimately brings about permanent mitotic arrest in the majority of cells.

HeLa Cells↗
PubMed1969

Time-lapse cinemicrographic studies of x-irradiated HeLa S3 cells. II. Cell fusion.

Analysis of time-lapse cinemicrographs of X-irradiated HeLa S3 cells has shown that the incidence of cell fusion was increased from 0.9% (following 1267 divisions) in control cells to an average of 22% (following 655 divisions) in cells irradiated with 500 rad doses of 220 kv X-rays. The incidence depended on the stage of the generation cycle at which the parent cells were irradiated. It was nearly constant in the first three postirradiation generations. Fusion occurred at all stages of the generation cycle, but preferentially during the first 20%. Cells undergoing fusion progressed more slowly through the generation cycle and had a higher probability of disintegrating than did irradiated cells that did not fuse. The occurrence of fusion was clonally distributed in the population. It took place only between sister (or closely related) cells. Protoplasmic bridges were often visible between sister cells prior to fusion. Giant cells arose only as a result of fusion. The incidence of multipolar divisions, though higher than in unirradiated cells, was only 5.5% in cultures irradiated with 500 rads. Fusion occurred following 85% of the multipolar divisions and was often followed by a multipolar division.

Cell Biology↗
PubMed1969

Variations in sulfhydryl, disulfide, and protein content during synchronous and asynchronous growth of HeLa cells.

The cellular contents of protein-bound and nonprotein sulfhydry (-SH) and disulfide (-SS-) groups were measured in both asynchronous and synchronous HeLa S3 cultures. About 90% of these groups are associated with proteins, the majority in the -SH form. The content of protein-bound groups, and hence the total content of -SH and -SS- groups (28 x 10(-15) moles/cell, or 1.1 x 10(-6) moles/g protein on average), changes in parallel with the protein content (which varies between 2 and 4 x 10(-10) g/cell) as asynchronous populations pass from the lag through the exponential to the stationary phase of growth. The concentration of nonprotein -SH groups, in contrast, increases 10-fold during lag phase and decreases in stationary phase; it follows the protein concentration closely during the exponential phase, at a level of about 2.8 x 10(-15) moles/cell. In synchronous cultures the protein content doubles during the cell cycle, possibly in an exponential fashion. The total -SH and -SS- content also doubles, but the rate of increase appears to fluctuate. The concentrations of the protein-bound groups show 2- to 3-fold fluctuations per unit protein: protein-bound -SH groups and mixed -SS- linkages rise to maxima while protein-bound -SS- groups fall to a minimum at the G(1)/S transition, and fluctuations in these groups occur again during G(2). In addition, the protein-bound -SH concentration falls continuously during the S phase. The nonprotein -SH concentration undergoes the largest (relative) fluctuations, dropping from 4 x 10(-15)moles/cell in early G(1) to about 0.4 x 10(-15) moles/cell (of standard protein content) at the end of G(1), and then rising to 30 times this value by the end of S.

Arginine↗