Biomedical subjects

R G Bristow

Publications and source records attributed to R G Bristow.

5 recordsLinked to original sources

PubMed1991

Role of transfection and clonal selection in mediating radioresistance.

Transfected oncogenes have been reported to increase the radioresistance of rodent cells. Whether transfected nononcogenic DNA sequences and subsequent clonal selection can result in radioresistant cell populations is unknown. The present set of experiments describe the in vitro radiosensitivity and tumorigenicity of selected clones of primary rat embryo cells and human glioblastoma cells, after transfection with a neomycin-resistance marker (pSV2neo or pCMVneo) and clonal selection. Radiobiological data comparing the surviving fraction at 2 Gy (SF2) and the mean inactivation dose show the induction of radioresistance in two rat embryo cell clones and one glioblastoma clone, as compared to untransfected cells. Wild-type and transfectant clones were injected into three strains of immune-deficient mice (scid, NIH, and nu/nu) to assay for tumorigenicity and metastatic potential. Only the glioblastoma parent line and its transfectant clones were tumorigenic. None of the cells produced spontaneous or experimentally induced metastases. Flow cytometric analyses indicated that the induction of radioresistance could not be attributed to changes in cell kinetics at the time of irradiation. Our results show that transfection of a neomycin-resistance marker and clonal selection can impart radioresistance on both normal and tumor cells. The work also indicates that altered radiation sensitivity does not necessarily correlate with changes in cell-cycle kinetics at the time of irradiation, tumorigenicity, or altered metastatic potential. Our findings have critical implications for transfection studies investigating determinants of cellular radiosensitivity.

Animals↗

PubMed1990

Comparison between in vitro radiosensitivity and in vivo radioresponse in murine tumor cell lines. II: In vivo radioresponse following fractionated treatment and in vitro/in vivo correlations.

Survival in the low-dose region of in vitro radiation survival curves for human tumor cell lines may be correlated with the expected clinical radiocurability of tumors of similar histopathological type. The present investigation examined this hypothesis using a series of transplantable murine solid tumors. The in vivo radioresponse of the tumors following fractionated dose (10 fractions of 2 Gy given at 4 hr intervals) and single dose (20 Gy) radiation treatment was measured by growth delay and tumor cell survival assays. The measurements of tumor cell survival were initiated either immediately or 8 hr after the end of radiation treatment. There was no evidence for repair of potentially lethal damage in vivo in any of the tumors. The measurements of in vivo response were compared to parameters of in vitro radiation survival curves for the same tumor cell lines, which were measured concurrently. The tumor cell survival following 10 fractions of 2 Gy correlated best with the measured in vitro survival at 2 Gy, although good correlations were also observed with two parameters calculated from the in vitro data; the value of alpha from fitting the linear-quadratic (LQ) model and the mean inactivation dose (MID). Correlations were also observed between specific growth delay measured in vivo following 10 fractions of 2 Gy and these in vitro parameters. Despite the correlations observed, the measured survival values following 10 fractions of 2 Gy in vivo did not agree quantitatively with the theoretical values predicted from the in vitro survival data assuming equal effect for each fraction. This discrepancy indicates that other factors also contribute to the overall response of a tumor to fractionated irradiation. Nevertheless, these findings support the idea that intrinsic radiosensitivity plays a significant role in determining the overall response of a tumor to fractionated irradiation and provides strong support for the concept of testing the in vitro radiation sensitivity of biopsy specimens as a predictive assay of clinical radiocurability.

Animals↗

PubMed1990

Comparison between in vitro radiosensitivity and in vivo radioresponse of murine tumor cell lines. I: Parameters of in vitro radiosensitivity and endogenous cellular glutathione levels.

Recent studies have suggested that differences in the initial low-dose region of the radiation survival curves for human tumor cells might explain the differences in clinical response of tumors to fractionated radiation treatment. In this study, which is described in two companion papers, we investigated this hypothesis directly using animal model systems. In the present paper we determined in vitro radiation survival curves for eight murine tumor cell lines of varying histopathological type and: (a) measured survival at the 2 Gy and 8 Gy dose levels, (b) fitted parameters to the linear quadratic and two component multi-target equation models of cellular survival and (c) calculated mean inactivation doses. We found that the choice of the data fitting procedure affected the absolute value, relative ranking, and power to discriminate between the cell lines of these calculated parameters. A detailed statistical study indicated that the measured surviving fraction at 2 Gy (SF2) was the best discriminant of intrinsic radiosensitivity between the eight tumor cell lines. When these same cell lines were assayed for intracellular glutathione (GSH) levels, no correlation was found between levels of GSH and the SF2 value. Determining the SF2 value may be the method of choice to describe the low-dose region of the radiation survival curve, as it precludes the necessity of choosing a model to fit the survival data, it has excellent discriminatory powers, and it represents the survival in the radiotherapeutically relevant region of the in vitro radiation survival curve. Furthermore, as demonstrated in the companion paper, it correlates with cell survival in the tumors following 10 fractions of 2 Gy given in vivo.

Animals↗

PubMed1989

Thyroid dose distribution in dental radiography.

The anatomic position and proven radiosensitivity of the thyroid gland make it an organ of concern in dental radiography. A calibrated thermoluminescent dosimetry system was used to investigate the absorbed dose (microGy) to the thyroid gland resultant from a minimum irradiated volume, intraoral full-mouth radiography technique with the use of rectangular collimation with a lead-backed image receptor, and conventional panoramic radiography performed with front and rear lead aprons. Use of the minimum irradiated volume technique resulted in a significantly decreased absorbed dose over the entire thyroid region ranging from 100% to 350% (p less than 0.05). Because this intraoral technique results in radiographs with greater image quality and also exposes the thyroid gland to less radiation than the panoramic, this technique may be an alternative to the panoramic procedure.

Equipment Design↗

PubMed1989

Technique-dependent decrease in thyroid absorbed dose for dental radiography.

A LiF thermoluminescent dosimetry (TLD) system, calibrated in the tissue of interest with the beam used for experimentation, was employed to investigate dosages (muGy) to the thyroid region of an anthropomorphic phantom resultant from two dental complete-mouth radiographic procedures. Both techniques were compared in terms of dosages associated with combinations of lead apron and thyroid collar shielding while using a 70-kVp or 90-kVp x-ray beam for a 20-film complete-mouth series. Lead shielding significantly decreased the dose to the thyroid using both techniques (p less than 0.05). The use of the 90-kVp beam resulted in a significant reduction in the thyroid absorbed dose when using the bisecting angle technique (p less than 0.05) but caused a significant increase in the thyroid absorbed dose when the paralleling technique was used (p less than 0.05). The implementation of higher kilovoltage techniques in dental offices must therefore be dependent on the radiographic technique employed.

Humans↗