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CELLULAR RADIOBIOLOGY

Objective

THE RISKS OF RADIATION TO MAN CANNOT BE STUDIED DIRECTLY BUT ARE INFERRED THROUGH STUDIES ON ANIMALS, PLANTS OR CELLS. IT IS NOT EASY TO INFER THE RESPONSE ON THE WHOLE ANIMAL FROM EFFECTS ON INDIVIDUAL CELLS BUT IT IS POSSIBLE TO STUDY THE RELATIVE BIOLOGICAL EFFECTIVENESS (RBE) OF RADIATIONS WITH DIFFERENT RATES OF ENERGY DEPOSITION. EXTRAPOLATION TO THE LOW DOSE-RATES USED IN THE NUCLEAR INDUSTRY IS VERY IMPORTANT AS IS THE BIOLOGICAL END POINT USED TO GIVE XPRESSION TO THE RADIOBIOLOGICAL EFFECT. THUS WE INTEND TO STUDY EXPERIMENTALLY THE EFFECTIVENESS OF NEUTRON RELATIVE TO GAMMA RADIATION ON INDUCED MUTATIONS, CHROMOSOME ABERRATIONS AND MALIGNANT TRANSFORMATIONS AS A FUNCTION OF DOSE AND DOSE RATE.
Results show no evidence of an IDRE for mutation at the hypoxanthine guanine phosphoribosyltransferase (HGPRT) locus when nondividing cells were irradiated with either 2.9 MeV neutrons or 3.2 MeV alpha particles. However, there was a small, but consistent trend towards an enhanced mutation frequency when cultures of dividing cells were irradiated with neutrons using a combination of low dose and low dose rate. Unfortunately, the sensitivity of the mutation assay is relatively poor and it was not possible to measure the mutation frequency at doses lower than 0.5 Gy.
These observations suggest that the IDRE effect seen in these experiments could be attributable to variations in radiosensitivity during the cell cycle.
HILL AND ELKIND HAVE SUGGESTED THAT REDUCTION IN DOSE RATE FOR FISSION-SPECTRUM NEUTRONS INCREASES THE TRANSFORMATION FREQUENCY SO WE WILL SEE IF THIS EFFECT CAN BE CONFIRMED IN THE MOUSE CELL LINE (C3H 10T 1/2) USED IN OUR LABORATORY. HOWEVER, SIMILAR EFFECTS OF DOSE RATE MIGHT WELL BE OBSERVED FOR MUTATION INDUCTION OR FOR CHROMOSOME ABERRATIONS AND STUDIES ON THESE END-POINTS MAY WELL SHEDLIGHT ON THE MECHANISM OF TRANSFORMATION. THE MOUSE CELLS ARE TETRAPLOID AND ARE NOT SUITABLE FOR MUTATION EXPERIMENTS AND SO WE INTEND TO USE CHINESE HAMSTER CELLS (V79 LINE) IN STATIONARY PHASE, FOR THESE STUDIES. FLOW CYTOMETRY AND THE DETERMINATION OF CHROMOSOME AND CHROMATID ABERRATIONS WILL BE USED TO MONITOR THE DISTRIBUTION OF CELLS IN THE CELL CYCLE AND ANY EFFECTS OF IRRADIATION ON THIS DISTRIBUTION. THIS WORK WILL BE EXTENDED TO HIGHER NEUTRON ENERGIES UP TO 15 MEV WHICH HAS SIGNIFICANCE FOR FUTURE EXPOSURES IN FUSION RESEARCH. THERE IS A NEED TO PRODUCE QUICKER MORE OBJECTIVE METHODS OF SCORING TRANSFORMATIONS.
IN CURRENT WORK AT HARWELL WE HAVE INDICATIONS OF CHANGES IN CELL-WALL PROTEINS IN TRANSFORMED CELLS AND WE INTEND TO INVESTIGATE THESE CHANGES WITH A VIEW TO DEVELOPING TESTS WHICH ARE LESS TIME CONSUMING AND LESS LABOUR INTENSIVE.

PROJECT 1: MUTATION AND CHROMOSOME ABERRATION.

A PROGRAMME OF EXPERIMENTS WILL BE CARRIED OUT ON THE EFFECT OF NEUTRON DOSE RATE ON MUTATION, CHROMOSOME ABERRATION AND CELL REPRODUCTIVE DEATH IN STATIONARY-PHASE MAMMALIAN CELLS. CHINESE HAMSTER V79 CELLS WILL BE USED. NEUTRON SOURCES TO BE USED INCLUDE: 15 MEV NEUTRONS (T(D,N) TO THE POWER OF 4 HE REACTION) FROM THE HARWELL COCKCROFTWALTON ACCELERATOR; A NEUTRON SPECTRUM WITH MEAN ENERGY ABOUT 2 MEV FROM THE BOMBARDMENT OF BERYLLIUM WITH 3 MEV DEUTERONS. DOSE-RATES FROM ABOUT 10 GY/H DOWN TO 0.05 GY/H WILL BE USED. A LIMITED PARALLEL PROGRAMME OF EXPERIMENTS WILL BE CARRIED OUT USING COBALT-60 GAMMA-RAY IRRADIATION.

PROJECT 2: CELL TRANSFORMATION.

THE EFFECT OF NEUTRON DOSE-RATE ON CELL TRANSFORMATION WILL BE STUDIED USING THE MOUSE CELL LINE (C3H 1OT 1/2). TWO NEUTRON SOURCES WILL BE USED, 15 MEV NEUTRONS FROM THE T(D,N) TO THE POWER OF 4 HE REACTION AND ALSO A FISSION-LIKE SPECTRUM FROM THE BE(D,N) REACTION USING 3 MEV DEUTERONS. DOSE-RATES FROM 3 GY/H TO 0.05 GY/H WILL BE USED.
THE INDUCTION OF TRANSFORMATION BY A FILTERED REACTOR NEUTRON BEAM OF ENERGY 24 KEV WILL ALSO BE MEASURED; THE DOSE RATE OF THIS BEAM IS LIMITED TO A SINGLE VALUE OF 0.02 GY/H. EXPERIMENTS WITH COBALT-60 GAMMA-RAYS WILL BE CARRIED OUT IN ORDER TO ESTABLISH THE RBE VALUES FOR THE VARIOUS NEUTRON RADIATIONS.

Funding Scheme

CSC - Cost-sharing contracts

Coordinator

United Kingdom Atomic Energy Authority (UKAEA)
Address
11 Charles Ii Street
SW1Y 4QP London
United Kingdom