INTER-RELATED STUDIES ON DOSE DEPENDANCE AND MECHANISMS OF RADIATION INDUCED CARCINOGENESIS ENVIRONMENTALLY INDUCED AND RADIATION PROMOTED CARCINOGENESIS

Cel

THIS GROUP HAS RECENTLY BEEN INVOLVED IN THE ESTABLISHMENT OF DIFFERENTIATED CULTURES OF HUMAN AND SHEEP THYROID, HUMAN COLONIC EPITHELIA AND HUMAN SKIN (FIBROBLASTS AND KERATINOCYTES). MANY OF THE CULTURES RETAIN MORPHOLOGICAL AND FUNCTIONAL CHARACTERISTICS OF THE ORIGINAL TISSUE AND FOLLOWING GAMMA IRRADIATION AT A WIDE RANGE OF DOSES HAVE BEEN SHOWN TO DEVELOP SEVERAL TRANSFORMED CHARACTERISTICS. THE PROJECT PROPOSED IS INTENDED TO INVESTIGATE THE CULTURE SYSTEMS, TO STUDY MECHANISMS OF RADIATION CARCINOGENESIS AND TO USE THE SYSTEMS TO STUDY THE DOSE DEPENDENCE OF THE TRANSFORMATION STEPS AND THE POSSIBLE SYNERGETIC EFFECTS OF KNOWN TUMOUR PROMOTORS AND SUSPECTED ENVIRONMENTAL CARCINOGENS ON IRRADIATED CELLS.
IF DEVELOPMENT OF THE CULTURE SYSTEMS FOR HUMAN TISSUES TO A HIGH LEVEL OF DIFFERENTIATION IS SUCCESSFUL THE PROJECT SHOULD ALLOW TISSUE SPECIFIC EFFECTS TO BE IDENTIFIED AND ANALYSED.
Interrelated studies on dose dependence and mechanisms of radiation induced carcinogenesis in environmentally induced and radiation promoted carcinogenesis has been carried out.

One of the major problems in the field of radiation protection is concern over induction of cancers in exposed humans. In order to study the carcinogenic effects of radiation in a systematic way it is clearly necessary to develop experimental systems which will allow the various stages of the carcinogenic process to be produced and quantified in a controlled manner. Ideally such systems should be based on human cells exposed to relevant doses of radiation which then undergo one or more definitive changes which can be quantified with respect to total dose, dose rate, radiation quality etc.
IN THE EARLY YEARS WORK WILL CONCENTRATE ON THE COLLECTION OF DATA USING SYSTEMS ALREADY ESTABLISHED IN THE LABORATORY, E.G. GASTRO-INTESTINAL TRACT AND SKIN, BUT IN LATER YEARS IT IS HOPED TO DEVELOP CULTURE SYSTEMS FOR THE EXAMINATION OF OTHER HUMAN TISSUES WHICH ARE OF CONCERN IN THE RADIATION PROTECTION FIELD, E.G. BREAST AND REPRODUCTIVE TISSUE. PRELIMINARY EXPERIMENTS WITH SOME OF THESE TISSUES HAVE COMMENCED BUT THEY REQUIRE CONSIDERABLE DEVELOPMENT TO OBTAIN TECHNIQUES FOR CULTURE OF MATERIALS RETAINING DIFFERENTIATED CHARACTERISTICS.
THE PROPOSED PROGRAMME IS AS FOLLOWS:
EARLY YEARS:
1. RADIATION DOSE RESPONSE CURVES FOR SURVIVAL AND TRANSFORMATION WILL BE GENERATED FOR PRIMARY CULTURES OF AVAILABLE HUMAN TISSUE, WHERE GOOD CULTURE TECHNIQUES HAVE ALREADY BEEN ESTABLISHED, E.G. SKIN AND COLON. PARTICULAR EMPHASIS WILL BE PLACED ON DETERMINING THE EFFECTS OF LOW LEVELS OF BETA AND GAMMA RADIATION, WHICH ARE CAUSING CONCERN IN RADIATION PROTECTION FIELDS. THE END-POINTS TO BE EXAMINED WILL INCLUDE CLONOGENIC SURVIVAL FUNCTION, EG. MUCOUS OR MELANIN PRODUCTION, LDH ISO-ENZYME PATTERN, DEVELOPMENT OF MALIGNANT PREKERATINS, IMMORTALITY, ANCHORAGE INDEPENDENCE AND LOSS OF CONTACT INHIBITION. IN COLLABORATION WITH THE MRC TOXICOLOGY UNIT IN CARSHALTON ANY POTENTIALLY TRANSFORMED CLONES WILL BE TESTED IN NUDE MICE FOR ABILITY TO PRODUCE TUMOURS.
2. CULTURE TECHNIQUES WILL BE DEVELOPED FOR TISSUES (HUMAN WHERE POSSIBLE) OF IMPORTANCE IN THE RADIATION PROTECTION FIELD. INITIALLY EFFORTS WILL CONCENTRATE ON MAMMARY TISSUE.
3. KNOWN TUMOUR PROMOTORS, EG. PHORBOL ESTERS, - WILL BE TESTED IN THE SYSTEM BOTH TO POTENTIATE THE RESPONSE AND TO STUDY MECHANISMS INVOLVED IN THE PRODUCTION OF THE VARIOUS TRANSFORMATION ENDPOINTS.
LATER YEARS:
1. THE DEVELOPMENT OF PRIMARY CULTURE SYSTEMS WILL PROCEED WITH THE AIM OF ACHIEVING MODEL TRANSFORMATION SYSTEMS FOR HUMAN RADIATION CARCINOGENESIS IN SPECIFIC TISSUES.
2. THE SEARCH FOR PROMOTORS AND SYNERGISTIC SUBSTANCES WILL CONTINUE AND IF THE METABOLIC STUDIES ON MECHANISMS ARE SUCCESSFUL IT SHOULD BE POSSIBLE TO USE SOME OF THE RADIATION INITIATED AND CHEMICALLY PROMOTED SEQUENCES TO TEST THEORIES OF POSSIBLE CARCINOGENESIS MECHANISMS.

Dziedzina nauki

Program(-y)

FP1-RADPROT 6C - Multiannual research and training programme (Euratom) in the field of radiation protection, 1985-1989

Temat(-y)

Data not available

Zaproszenie do składania wniosków

Data not available

System finansowania

CSC - Cost-sharing contracts

Koordynator

SAINT LUKE'S HOSPITAL

Wkład UE

Brak danych

Adres

HIGHFIELD ROAD RATHGAR
DUBLIN 6
Irlandia

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