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Biomedical subjects

M R Raju

Publications and source records attributed to M R Raju.

At least 55 records · Page 3Linked to original sources

Biological effects of pion therapy beams: I. Cultured cells.

The results of cell killing by pion beams of different peak widths, ranges and sizes used in therapy are reported. Cultured hamster cells (V79) suspended in gelatin were used. The results indicate that: 1) there are no significant differences in cell-killing between pion beams of different ranges but of the same peak width; 2) there is a slight decrease in biological effectiveness with increasing peak width; and 3) the range-modulation functions used to produce uniform cell-killing are satisfactory for intermediate-range pion beams, but slight corrections may be required for shorter- and longer-range pion beams.

Animals↗

Residual radiation damage in the mouse foot after exposure to argon ions and retreatment with X rays.

The results of radiation treatment as visible residual damage are reported for acute skin reaction and foot deformity in mice exposed to argon ions. Two groups of 40 mice each were exposed to argon ions at the plateau and peak center of a 10-cm-wide Bragg peak to a fixed dose of 1200 and 1300 rad, respectively. A third group of 40 mice was exposed to 1750 rad of 250-kVp X rays while the fourth group was kept as controls. The acute skin reactions were scored for 60 days and foot deformity at 8 months after exposure. These mice were reexposed 8 months after the first exposure to graded doses of X rays ranging from 1200 to 2500 rad. Acute skin reactions were scored again for 60 days and foot deformity 8 months after the second exposure to graded doses of X rays. The results showed that no significant visible residual damage of the first treatment of either argon ions or X rays was observed after a second irradiation with X rays for acute skin reaction. For the end point deformity, however, residual damage of the first treatment was observed. The residual damage for foot deformity for argon ions does not seem to be higher than for X rays when the doses of first treatment with argon ions and X rays were matched to produce nearly uniform effect. The results also suggest a threshold dose to show the residual damage of the first treatment.

Acute Disease↗

Radiobiology of pions at LAMPF.

Recent radiobiology data for pion beams used in therapy are presented. The biological systems used were cultured cells suspended in gelatin and intestinal crypt assay. The importance of fast neutrons from pion stars in large treatment volumes is discussed. The data for compensating the depth dose distribution to produce uniform cell killing across the peak region are presented. The changes in biological effectiveness with peak width for pion beams (unlike heavy ions) are small because of fast neutron contribution from pion stars. The need for innovative radiobiology programs to guide high-LET radiotherapy is discussed.

Animals↗

Residual radiation damage in the mouse foot after exposure to heavy particles.

Mice receiving a first treatment with graded doses of various heavy charged particles (protons and heavy ions) to one of their hind legs were re-exposed to a fixed dose of x rays eight months later to study the "memory" of residual damage from the first treatment. No significant memory of the first radiation exposure was observed for acute skin rection. However, there is an indication of memory for foot deformity. The results do not seem to indicate any significant differences in memory after exposure to 60Co gamma rays compared with protons or heavy ions, if biological effectiveness of the doses is taken into consideration.

Animals↗

Ploidy and DNA distribution analysis of spontaneous dog tumors by flow cytometry.

Ploidy and DNA content distributions were measured for 68 biopsy specimens of spontaneous (solid) dog tumors using flow cytometry analysis of mithramycin-stained cells. The tumor ploidy (i.e., DNA index values) ranged from 1.0 to 4.0 (diploid = 1.0), with a mean of 1.4. More than 80% of the tumors had elevated G0-G1 peak DNA contents and were classified heteroploid, similar to human solid tumors. Six mammary carcinomas and osteosarcomas had bimodal G0-G1 peaks. Based on flow cytometric data and pathology criteria, it was observed that: (a) the percentage of tumor S-phase cells tended to increase with increasing DNA index; and (b) for a given DNA index, the percentage of S-phase cells was lower for well-differentiated tumors and higher for poorly differentiated tumors. The inherent scattering of the DNA content and DNA distribution data between different tumor types limited the usefulness of these data for classifying tumors. The results suggest that improved classification of cytologically different tumors and tumor subsets might be achieved by simultaneous flow measurement of DNA content and DNA distribution information with an additional parameter that detects the cytological differentiation state.

Animals↗

Correlation of the growth of Chinese hamster V279-17lb multicellular spheroids with cytokinetic parameters.

The volumes of Chinese hamster V279-17lb multicellular spheroids grown in spinner culture were measured and correlated to DNA distribution and cell volume distribution information. Spheroid growth curves were obtained over a 21-day period using both electronic cell volume measurements and microscope micrometer sizing. The spheroids were collected from the aperture tube after electronic sizing, and single cell suspensions were prepared via trypsinization. Saline-washed cells were then stained with mithramycin and analyzed as unfixed or ethanol-fixed cells for both cell volume and DNA fluorescence measurements. Spheroid growth was determined to have an initial 8- to 9-day rapid growth phase, and a slow phase from 10 to 21 days. The single cell volume distributions of cells obtained from spheroids were dependent on spheroid volume and the relative proportions of small volume noncycling cells to large volume cycling cells comprising the spheroids were also dependent on spheroid volume. DNA distribution data and dual parameter DNA distribution cell volume contour patterns obtained for single cells dissociated from spheroids were closely related to the measured spheroid volume and revealed that the fraction of small, hypoxic G0-like cells was greatest in old, large spheroids.

Animals↗

Flow cytometric applications to tumour biology: prospects and pitfalls.

A brief review of cytometry instrumentation and its potential applications in tumour biology is presented using our recent data. DNA distribution measurements of cells from spontaneous dog tumours and cultured cells after exposure to X-rays, alpha particles or adriamycin are shown. The data show that DNA fluorescence measurments have application in the study of cell kinetics after either radiation or drug treatment. Extensive and careful experimentation is needed, however, to utilize the sophisticated developments in flow cytometry instrumentation.

Animals↗

Radiobiologic properties of pions and heavy ions. A comparison.

1. Depth-dosage distributions of pions and heavy ions are similar, but the dose fall-off near the range is much steeper for heavy ions compared to pions. 2. Radiation quality and hence biologic effects of heavy ion beams in the peak region depend only on peak width, whereas for pion beams because of fast neutrons from stars, the radiation quality may depend not only on peak width but also on beam size. 3. For neon and argon ions, the biologic effects of fractionated doses in proliferating cells are found to be more effective than for single doses. Such an effect was not observed for either fast neutrons or for pions. 4. Radiobiologically, pion beams are similar to helium and carbon ions.

Animals↗

OER and RBE for negative pion beams of different peak widths.

Experimental data on survival curves for pion because of different peak widths under aerobic and hypoxic conditions are reported. Metabolic depletion of oxygen by the Chinese hamster cells (line V79) was used to obtain hypoxia. The results indicate that the RBE at the beam entrance (plateau) is approximately 1.0. When the Bragg peaks were broadened to widths of 1.3, 7.8, and 10.5 cm (at the 80% dose level), the RBE (50% cell survival) at the peak centres was 1.7, 1.6, and 1.2, respectively. The OER at the entrance was 2.4 compared with about 2.9 for X rays. The OER was independent of the survival level at which it was measured. The OER at the peak centres at widths of 1.3, 7.8, and 10.5 cm was 2.1, 2.4, and 2.2, respectively. These results indicate that, although the RBE at the centre of the 10.5 cm wide peak was significantly lower than at the centres of the 1.3 and 7.8 cm peaks, the OER values are similar for all peak widths used in this study.

Animals↗

A heavy particle comparative study. Part I: depth-dose distributions.

The results of a comparative study of heavy particles of interest in radiotherapy, with peaks spread over a depth of 10 cm, are reported in four parts. The introduction to this study and the depth-dose distributions of the particles, (n, pi-, p, He, C, Ne, and Ar ions) are reported herein. The results indicate that protons give the best localization of dose. The degree of localization of dose with heavy ions is reduced with increasing charge on the ion. For ranges less than 15cm, heavier ions such as neon and argon still have favourable dose localization; however, for ranges in excess of 15 cm, heavy ions such as argon are unfavourable but superior to fast neutrons because penetration can be controlled by modulation of energy or range.

Argon↗

A heavy particle comparative study. Part II: cell survival versus depth.

Cell-survival measurements with depth of penetration were made for a series of incident doses of proton, helium, carbon, neon, argon, negative pion, neutron, and 60Co photon beams. Cultured human cells (T1) suspended in a gel-containing medium were used, and the measurements were found to be very useful in facilitating the design of ridge filters to produce iso-effects in the region of interest. Heavy charged particle beams (proton, helium, carbon, neon, and negative pion) were found to produce similar cell killing with depth of penetration. Because of saturation effects at higher LET, argon ions were less effective in killing aerated cells at depth, compared with other heavy charged-particle beams. Cell killing at depth in the region of interest, compared with that at the entrance, was not significantly different for single-field exposures when the Bragg peaks were broadened to cover a width of 10 cm. However, when two opposed fields with overlapping peaks were used, a large enhancement in killing was obtained in the peak region.

Argon↗

A heavy particle comparative study. Part III: OER and RBE.

The results of a comparative study of heavy particles of interest in radiotherapy are reported in four parts. In this Part III, cell-survival measurements under aerobic and hypoxic conditions were made for various heavy particle beams. For heavy charged-particle beams, the measurements were made at the beam entrance (plateau), peak centre (10 cm wide peaks), and distal peak (1 cm from dose fall-off). Chinese hamster cells (V79) were used. Metabolic depletion was used to obtain hypoxia. The results indicate that the differences in RBE between the entrance region and peak are not very large when the Bragg peaks are broadened to 10 cm. The RBE for argon ions remains the same at the entrance and peak centre, and the RBE at the distal side of the Bragg peak is significantly reduced compared to the peak centre and entrance region because of saturation effects at high LET. The OER for protons is not significantly different from that for X rays. The OER for helium ions, carbon ions, and negative pions is larger, for neon ions is similar, and for argon ions is smaller when compared with fast neutrons. The OER values for heavy ions are higher than expected and could be due to a large delta-ray penumbra associated with the energy deposited by energetic heavy ions. The oxygen effect may depend upon energy deposition over distances of the order of nanometers.

Argon↗