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RADIOBIOLOGICAL DAMAGE INDUCED INTO MAMMALIAN AND HUMAN CELLS BY LOW ENERGY MONOENERGETIC PROTONS AND CALCULATIONS OF THE RBE FACTORS FOR RISK ESTIMATIONS

Objective

PROTONS HAVE ATTRACTED THE INTEREST OF RADIOTHERAPISTS, RADIOBIOLOGISTS AND PHYSICISTS, AS A RADIATION OF POTENTIAL USE IN THE TREATMENT OF CANCER MAINLY BECAUSE OF THEIR PROPERTY OF HAVING A VERY SHARPLY DEFINED EFFECTIVE RANGE IN TISSUE. SINCE 1957 CLINICAL APPLICATIONS HAVE TAKEN AT VARIOUS CENTERS AROUND THE WORLD USING PROTON BEAMS WITH ENERGY UP TO 100 MEV OR EVEN HIGHER; THIS WORK HAS BEEN EXTENSIVELY REVIEWED (RAJU 1980).

THOUGH PARALLEL RADIOBIOLOGICAL WORK HAS BEEN CARRIED OUT IN THE SAME RANGE OF HIGH ENERGIES (HALL ET AL 1980, TAPPER ET AL 1977) WORK WITH LOW ENERGY BEAMS IS SCARCE (BETTEGA ET AL 1979, TAKATSUJI AND TAKEKOSHI 1983) ESPECIALLY IN THE CASE OF SURVIVAL DATA (BETTEGA ET AL 1983, PERRIS ET AL 1986). RADIOBIOLOGICAL EXPERIMENTS WITH LOW ENERGY BEAMS ARE PERFORMED ACCORDING TO THE "TRACK-SEGMENT" METHOD (NEARY 1970) IN WHICH THE MONOENERGETIC PROTON BEAM PASSES THROUGH A CELL MONOLAYER DEPOSITING ENERGY WITH A WELL DEFINED LET VALUE. THUS THE BIOLOGICAL DAMAGE CAN BE STUDIED AS A FUNCTION OF LET; THE NEED FOR SUCH DATA HAS BEEN STRESSED BY SEVERAL AUTHORS (E.G. BARENDSEN 1978). THE RESULTS OF SUCH EXPERIMENTS RELATE NOT ONLY TO THE USE OF PROTON BEAMS IN RADIOTHERAPY BUT THEY ARE ALSO USEFUL FOR THE EVALUATION OF RADIOBIOLOGICAL MODELS WHICH PREDICT CELL SURVIVAL AS A FUNCTION OF LET, FOR THE EVALUATION OF THE EVENT SIZE (KELLERER AND ROSSI 1972) OR OTHER PHYSICAL PARAMETERS (KATZ ET AL 1971) AS WELL AS FOR THE ESTIMATION OF RADIATION RISK FOR RADIATION PROTECTION PURPOSES.

THE PROPOSED WORK AIMS TO GATHER RADIOBIOLOGICAL DATA RELATED TO THE ACTION OF IONISING RADIATIONS IN CONJUNCTION WITH RADIATION QUALITY AND DOSE RATE, THE TWO PRIMARY FACTORS AFFECTING THE ACTION OF IONIZING RADIATION IN BIOLOGICAL SYSTEMS.
Radiobiological damage induced in mammalian and human cells by low energy monoenergetic protons has been studied and relative biological effectiveness (RBE) factors have been calculated for risk estimations.
PROTON AND DEUTERIUM BEAMS PRODUCED BY THE TANDEM VAN DE GRAAFF ACCELERATOR OF THE NATIONAL RESEARCH CENTER FOR NATURAL SCIENCES (NSNRC) DEMOKRITOS, AND ALPHA-PARTICLES FROM AN AM-241 WILL BE USED TO PROVIDE INFORMATION RELATED TO THE SPATIAL DEPENDENCE OF SUBLESIONS TO FORM EVENTS RELATED TO THE RADIOBIOLOGICAL DAMAGE OF THE GENETIC APPARATUS OF THE MAMMALIAN CELLS, THAT IS DNA SINGLE OR ACENTRIC TYPE, CHROMATID ABERRATIONS INCLUDING SISTER CHROMATID EXCHANGES (SCE), MICRONUCLEI FORMATION (MN). THE USE OF A VARIETY OF DIFFERENT SECTIONS OF THE GENETIC APPARATUS AND THE ASSESSMENT OF THE RELATIVE EFFICIENCY OF EACH ONE AS A PARAMETER FOR RADIATION DAMAGE AND RISK ESTIMATION IN CONJUNCTION WITH PROBLEMS ASSOCIATED WITH SPATIAL AND TIME DEPENDENCE. FURTHERMORE, INSIGHT INTO THE SEQUENTIAL EVOLUTION AND INTERRELATIONSHIP CAN BE OBTAINED.

THESE EFFECTS ON THE GENETIC APPARATUS WILL BE MADE IN PARALLEL WITH SURVIVAL EXPERIMENTS WITH A FINAL AIM OF DETERMINING THE RBE VALUES RELATIVE TO GAMMA-RAYS, OVER A WIDE RANGE OF LOW ENERGY MONOENERGETIC PROTON BEAMS, FOR THE ABOVE MENTIONED INDUCED LESIONS. THE DATA WILL EVENT FRACTION, D THE DOSE AND ALPHA, BETA ARE COEFFICIENTS TO BE DETERMINED. THE DETERMINATION OF ALPHA AND BETA AND THEIR UNCERTAINTIES WILL BE CARRIED OUT WITH A COMPUTER PROGRAM WHICH ALSO ESTIMATES THE GOODNESS OF FIT. D WILL BE ESTIMATED ALSO AS "MEAN INACTIVATION DOSE D" (KELLERER 1965) WHICH MEASURES THE OVERALL REACTION OF THE CELLS OVER THE ENTIRE RANGE OF THE DOSE.

AS EXPERIMENTAL MATERIAL V-79 CHINESE HAMSTER CELLS, PRIMARY HUMAN FIBROBLAST CULTURES AND AMIOTIC CELLS WILL BE USED. THESE CELLS GROW AS A MONOLAYER PERMITTING THE BEST POSSIBLE HOMOGENEITY IN THE CASE OF LOW ENERGY PROTONS. IN THE MONOLAYER THESE CELLS STRONGLY ADHERE TO THE CARRIER SURFACE AND BECOME RATHER FLATTENED WITH A THICKNESS OF THE ORDER OF 6 MICROMETER.

CULTURAL AND EXPERIMENTAL CONDITIONS HAVE BEEN DESCRIBED IN PREVIOUS PUBLICATIONS OF THE GROUP (SIDERIS ET AL 1981, PERRIS ET AL 1986). INFORMATION RELATED TO THE ACCELERATOR OF THE NRCNS DEMOKRITOS AND THE EXTRACTION OF PROTONS AND DEUTERONS FROM THE VACUUMM TO AIR, AS NEEDED IN SUCH EXPERIMENTS, MAY BE FOUND IN OUR PREVIOUS PUBLICATIONS (KATSANOS ET AL 1976 AND 1986).

Funding Scheme

CSC - Cost-sharing contracts

Coordinator

GREEK ATOMIC ENERGY COMMISSION
Address
Phys.sciences "Democritus" Mr.a.kappas / Po Box 60228
10 Athinai
Greece