Print Email Facebook Twitter Influence of the H-ras oncogene on radiation responses of a rat rhabdomyosarcoma cell line 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 cellanimal modelanimal tissuecell culturecell killingcell survivalcell viabilitycontrolled studydose responsegastrocnemius musclegenetic transfectionhumanhuman cellirradiationnonhumanoncogene h raspriority journalradiation dose fractionationradiation injury repairradiation responseradiosensitivitytumor growth3T3 CellsAnimalCell DivisionCell LineCell SurvivalCesium RadioisotopesDose-Response Relationship, RadiationGamma RaysGenes, rasHumanMiceRadiation ToleranceRatsRhabdomyosarcomaSarcoma, ExperimentalTransfection To reference this document use: http://resolver.tudelft.nl/uuid:e6d7da95-d550-4a81-8afc-71143d12cba2 TNO identifier 231843 ISSN 0008-5472 Source Cancer Research, 52 (11), 3073-3082 Document type article Files To receive the publication files, please send an e-mail request to TNO Library.