Relative biological effectiveness of proton medical beam at Moscow synchrotron determined by the Chinese hamster cells assay.

PURPOSE: Assessment of relative biological effectiveness (RBE) of the proton medical beam at Moscow synchrotron. METHODS AND MATERIALS: The study was performed at Moscow proton medical facility (Institute for Theoretical and Experimental Physics). Relative biological effectiveness of the synchrotron proton beam was assessed at the entry of the unmodulated 179 MeV beam and in the center of spread out Bragg peak (SOBP), from measurements of the survival of Chinese hamster cells (clone 431). Gamma-radiation of 60Co was used as a reference source. RESULTS: According to the linear regression model, mean RBE values at 37% survival level were found to be 1.10 +/- 0.04 at the beam entry and 1.14 +/- 0.05 in the center of SOBP. Values of RBE obtained using the linear-quadratic model for 10% and 37% survival levels were 1.09 and 1.07, respectively, at the beam entry and 1.07 and 1.08, respectively, in the center of SOBP. CONCLUSIONS: The data obtained indicate that (a) the RBE values at the entry of the unmodulated beam and at the center of the SOBP are in close agreement, with an average of about 1.10; (b) protons are radiobiologically somewhat more effective than 60Co gamma rays; and, (c) high pulse dose rate of the medical beam does not significantly affect biological effects of the beam.

[The effect of prolonged gamma irradiation at a decreasing dose rate on survivability and gene mutation induction in cultured Chinese hamster cells]. / Vliianie protiazhennogo gamma-oblucheniia so spadaiushchei moshchnost'iu dozy na vyzhivaemost' i induktsiiu gennykh mutatsii v kul'tiviruemykh kletkakh kitaiskogo khomiachka.

Continuous gamma irradiation at decreasing dose rate was shown to be less effective than acute exposure with regard to the lethal effect and frequency of mutations of resistance to 6-thioguanine in cultured Chinese hamster cells. The cell population subjected to continuous irradiation was more radioresistant than the intact one. Lethal and genetic effects of continuous irradiation at decreasing dose rate were mainly determined by the contribution of the radiation dose received during the first 24 h of exposure.

[Mutations of resistance to 6-thioguanine following roentgen irradiation and subsequent treatment with cytosine arabinoside combined with hydroxyurea in Chinese hamster cells in the G1 phase]. / Mutatsii rezistentnosti k 6-tioguaninu posle rentgenovskogo oblucheniia i posleduiushchei obrabotki tsitozinarabinozidom v sochetanii s oksimochevinoi kletok kitaiskogo khomiachka v G1 faze.

A study was made of the effect of two-hour treatment of Chinese hamster cells with cytosine arabinoside (AraC) combined with hydroxyurea (HU) at the G1 phase of the cell cycle on lethal and mutagenic effects of X-radiation (50 to 400 cGy). The inhibitors were shown to increase a spontaneous mutation level of the resistance to 6-thioguanine: this increase augmented by 3 times as the time the treatment increased from 1-2 to 6 h. However, while sharply enhancing the inactivating effect of X-radiation (the enhancement coefficient was 2.6) Arac+HU caused an additive, or a somewhat lesser, effect as estimated by the yield of mutations. It is suggested that AraC combined with hydroxyurea fail to modify the radiation-induced premutation damages.

[Cytogenetic effect of irradiation and subsequent cytosine arabinoside and hydroxyurea treatment on Chinese hamster cells in the G1 phase of the cell cycle]. / Tsitogeneticheskii éffekt oblucheniia i posleduiushchei obarbotki tsitozinarabinozidom i oksimochevinoi kletok kitaiskogo khomiachka v G1-faze kletochnogo tsikla.

A two-hour treatment of Chinese hamster cells at the G1 stage of the cell cycle with arabinoside cytosine combined with hydroxyurea after X-irradiation (50-300 cGy) produced a 2- to 4-fold increase in the frequency of chromosome aberrations. The mitotic selection method was used to synchronize the cells. The potentiating effect of the inhibitors, that was estimated by the yield of centric exchanges, decreased with increasing radiation dose. It is suggested that DNA repair processes determining a linear component of the dose-response curve are modified within the dose-range under study.

[Induction of mutations resistant to 6-thioguanine by fast neutrons in cultured Chinese hamster cells]. / Induktsiia mutatsii rezistentnosti k 6-tioguaninu bystrymi neitronami v kul'ture kletok kitaiskogo khomiachika.

A study was made of induction of mutations, resistant to 6-thioguanine (TGr), and reproductive death of Chinese hamster cells after irradiation by fission-spectrum fast neutrons (mean energy of 0.75 MeV) with doses of 10-130 cGy. A high relative biological effectiveness (RBE) of fast neutrons was shown. The maximum RBE values (13-16) were within the dose range inducing minimum mutagenic and lethal effects. RBE decreased with the dose increase. Inspite of high mutagenic effectiveness of neutrons, estimated according to TGr mutation frequency per cell per dose unit, their relative mutagenic effectiveness, estimated per cell per one lethal event, did not substantially differ from that of X-radiation.

[Gene mutations, chromosome aberrations and survival after the x-ray irradiation of a Chinese hamster cell culture protected by cysteamine]. / Gennye mutatsii, aberratsii khromosom i vyzhivaemost' posle rentgenovskogo oblucheniia kul'tury kletok kitaiskogo khomiachka v usloviiakh zashchity tsisteaminom.

The protective effect of cysteamine against 6-thioguanine-resistance (TCr) mutations, chromosome aberrations and inactivation caused by X-ray in cultured cells of Chinese hamster (clone 431) has been studied. The dose-effect curves have been obtained under irradiation condition without protector and with it. Dose-modifying factor of 2 was calculated for chromosome aberrations and cells inactivation and 2,8 for TCr mutations. It is supposed that the cysteamine acts on the general mechanisms involved in damages realization which results in gene mutations, chromosome aberrations and cell inactivation.

[Patterns in the x-ray induction of mutations in resistance to 5-thioguanine in Chinese hamster cell cultures studied using cysteamine]. / Izuchenie zakonomernostei induktsii rentgenovymi luchami mutatsii rezistentnosti k 6-tioguaninu v kul'turakh kletok kitaiskogo khomiachka v usloviiakh primeneniia tsisteamina.

X-ray induction of 5-thioguanine resistance mutations and the protective effect of cysteamine were studied in cultured cells of chinese hamster clone 431. Expression of mutations was studied for 8--10 days of post-irradiated growth, when cells surviving radiation at doses 200, 400, 600, 800 R were passing from 3 to 12 generations. The maximum frequency of induced mutations was found after 3-5 generations. After reaching the maximum, the number of registered mutations decreased with the number of cell generations. Pre-irradiated treatment with 5mM cysteamine decreased induction of mutations 2--4 times when using doses 200--800 R. The frequency of mutations induced by mere radiation increased non-linearly with increasing doses, while in the presence of cysteamine the linear dose dependence was observed.

[The effect of cysteamine on x-ray induction of mutations resulting in resistance to 8-azaguanine in Chinese hamster cells in vitro]. / Vliianie tsisteamina na induktsiiu rentgenovymi luchami mutatsii rezistentnosti k 8-azaguaninu v kletkakh kitaiskogo khomiachka in vitro

The survival of Chinese hamster cell was increased after the administration of cisteamine (at doses of 1,25; 2,5 and 5,0 mM/ml) in the culture for 15--20 min. before X-irradiation (600r). In the same experiment the protector decreased the rate of induced Ag-resistance gene mutations.