Title
Influence of the H-ras oncogene on radiation responses of a rat rhabdomyosarcoma cell line
Author
Hermens, A.F.
Bentvelzen, P.A.J.
Instituut voor Toegepaste Radiobiologie en Immunologie TNO
Publication year
1992
Abstract
Rat R2k rhabdomyosarcoma cells were transfected with the human H-ras oncogene, which resulted in increased resistance to cell kill in vitro by a single dose of 137Cs γ-rays. A subline carrying one oncogene showed an increase in the quasi-threshold dose (D(q)) from 0.88 to 1.48 Gy. Another subline containing six oncogenes not only had an increased D(q) of 1.59 Gy but also showed an increase in the dose reducing cell survival to a fraction of e-1 = 0.37 (D0) from 1.25 to 1.76 Gy. Analysis of the cell survival data according to the linear-quadratic formalism indicated that a decrease in the value of the coefficient of the linear component α is associated with a H-ras-mediated increase in radioresistance. In fractionated irradiation experiments it was observed that with a dose of 1 Gy/fraction a 1.8 times higher dose for an isoeffect of 10% cell survival (D10) was needed for a subline with one H-ras oncogene, while with fraction doses of 2 or 4 Gy only a 1.2 times higher D10 was found. This indicates a more efficient repair of radiation-induced damage in the transfected subline. Tumors arising in the rat gastrocnemius muscle inoculated with cultured cells were irradiated with different doses of 300-kV X-rays. A single dose of 45 Gy was found to result in a 6% cure rate for the subline containing one H-ras oncogene and a 32% for the parental line. When a priming dose of 45 Gy was followed by fractionated irradiation with 1 Gy/fraction, an extra dose of 51 Gy would be needed to obtain a 75% cure rate for the transfected subline. An extra dose of only 10 Gy would be needed for the parental line. The percentage cure per unit of dose for the parental line irradiated with 1 Gy/fraction was estimated to be 4.3% · Gy-1, whereas for the transfected tumor line it was 1.4% · Gy-1. This means that a 3.0 times higher cumulated absorbed dose would be needed for enhancing the cure rate from 32% to 75% in the subline with H-ras than for the parental line. With 2 Gy/fraction the difference in extra doses required for obtaining isolevels of cure rates was found to be small, a factor of 1.4. The results indicate that in the course of fractionated irradiation with 1 Gy/fraction, in vivo repair is much more efficient in the transfected subline. Chemicals/CAS: Cesium Radioisotopes
Subject
animal cell
animal model
animal tissue
cell culture
cell killing
cell survival
cell viability
controlled study
dose response
gastrocnemius muscle
genetic transfection
human
human cell
irradiation
nonhuman
oncogene h ras
priority journal
radiation dose fractionation
radiation injury repair
radiation response
radiosensitivity
tumor growth
3T3 Cells
Animal
Cell Division
Cell Line
Cell Survival
Cesium Radioisotopes
Dose-Response Relationship, Radiation
Gamma Rays
Genes, ras
Human
Mice
Radiation Tolerance
Rats
Rhabdomyosarcoma
Sarcoma, Experimental
Transfection
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TNO identifier
231843
ISSN
0008-5472
Source
Cancer Research, 52 (11), 3073-3082
Document type
article