Skip to main content

ADAPTIVE RESPONSE TO LOW DOSES OF RADIATION : STUDIES IN HUMAN CELLS OF A POSSIBLE RADIATION STIMULATED REPAIR

Objective

IN THE NEXT FOUR YEARS THE RESEARCH PROJECT WILL BE FOCUSED ON THE INTERATION BETWEEN LOW CHRONIC DOSES OF RADIATION AND SUBSEQUENT TREATMENTS WITH EIGHER ACUTE DOSES. THIS PROJECT WILL INCLUDE (SEE BELOW9 STUDIES ON:
A) THE MECHANISMS OF CHROMOSOME ABERRATION FORMATION
B) THE FACTORS AFFECTING THE REPAIR OF GENETIC DAMAGE
C) THE RELATIONSHIPS BETWEEN DIFFERENT TYPES OF GENETIC DAMAGE
D) THE RELATIONSHIPS BETWEEN MUTAGEN TREATMENT IN VITRO AND IN VIVO.
The adaptative response (AR) has been defined as the reduction of clastogenic damage observed in human lymphocytes which were cultivated in tritiated thymidine (3HdThd) and subsequently exposed to high doses of X-rays. Several features of this adaptive response in human lymphocytes have been studied.
THE RESEARCH WILL BE CARRIED OUT ACCORDING TO THE FOLLOWING EXPERIMENTS:
1.-HUMAN LEUKOCYTES IN VITRO (OR CULTURED HUMAN FIBROBLASTS) WILL BE EXPOSED TO A FIRST TREATMENT WITH EITHER A LOW DOSE OF IONIZING RADIATIONS (UP TO 20R) OR A LOW CONCENTRATION OF TRITIATED THYMIDINE (INCORPORATED HTDR WILL PRODUCE A CHRONIC IRRADIATION). SUBSEQUENTLY, THE CULTURES WILL BE EXPOSED TO A SECOND TREATMENT WITH X-RAYS AT VARIOUS TIMES PRIOR TO FIXATION. THE CELLS EXPOSED TO THE TWO TREATMENTS WILL BE COMPARED WITH THOSE WHICH RECEIVED ONLY THE SECOND TREATMENT FOR THE FREQUENCY AND TYPE OF INDUCED GENETIC DAMAGE. IN A FIRST SERIES OF EXPERIMENTS ONLY CHROMATID ABERRATIONS WILL BE TAKEN INTO ACCOUNT. IN SUBSEQUENT EXPERIMENTS THE COMPARISON WILL BE EXTENDED TO OTHER BIOLOGICAL PARAMETERS SUCH AS UNSCHEDULED DNA SYNTHESIS. DNA STRAND BREAKS, MITOTIC DELAY AND CELL LETHALITY. IN SELECTED EXPERIMENTS, THE DISTRIBUTION OF BREAKS BETWEEN AND WITHIN CHROMOSOMES, THE RELATIVE FREQUENCY OF THE VARIOUS TYPES OF ABERRATIONS AND THE RELATIONSHIPS BETWEEN CHROMOSOME-DAMAGE AND MITOTIC DELAY WILL ALSO BE ANALYSED.

2.-THE SAME EXPERIMENTS PREVIOUSLY OUTLINED WILL BE REPEATED ON LYMPHOCYTES OF PATIENTS WHO, FOR EITHER OCCUPATIONAL OR MEDICAL REASONS, WERE EXPOSED TO RELATIVELY HIGH DOSES OF IONIZING RADIATION. OBVIOUSLY IN THESE EXPERIMENTS THE IN VIVO EXPOSURE IS EQUIVALENT TO THE FIRST TREATMENT DESCRIBED IN 1.
SIMILAR EXPERIMENTS WILL ALSO BE PERFORMED IN MICE EXPOSED (FIRST TRETMENT) TO LOW DOSES OF IONIZING RADIATIONS OR TO CHRONIC INTERNAL IRRADIATION WITH HTDR.

3.-THE SAME EXPERIMENT DESCRIBED IN 1 WILL BE CARRIED OUT ON CELL LINES WITH VARIOUS REPAIR DEFECTS.

Funding Scheme

CSC - Cost-sharing contracts

Coordinator

Università degli Studi di Roma 'La Sapienza'
Address
Piazzale Aldo Moro 5
00185 Roma
Italy