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(Mechanisms and secondary factors involved in the induction of radiation transformation in vitro): Comprehensive progress report

Technical Report ·
OSTI ID:6935408
We have previously shown that /sup 125/Iododeoxyuridine (/sup 125/IdUrd) and /sup 3/H-thymidine are more effective than x-rays in inducing malignant transformation when the results are normalized for survival. We have now observed a similar phenomenon for the induction of specific gene mutations in TK6 human lymphoblastoid cells. The results of parallel transformation experiments with tritiated water suggest that the enhanced efficiency of /sup 3/H-thymidine as compared with x-rays is due to a higher RBE of the tritium beta particle for mutagenesis and transformation, rather than to the fact that the radioactive decay occurs within the DNA molecule. Studies of the cell cycle specificity for the induction of cell killing and mutagenesis by /sup 125/IdUrd indicate that late S-phase cells are more radiosensitive than early S-phase cells to the localized deposition of energy characteristic of /sup 125/I decay. Cellular localization studies have shown that /sup 125/I decay must occur in close proximity to cellular DNA in order to produce mutations; /sup 125/IdUrd was very mutagenic in cells which incorporated it into DNA, but not in cells in which it remained in the acid soluble pool. Unexpectedly, a similar result has emerged from preliminary experiments with /sup 131/I (an energetic beta/gamma emitter); virtually no cytotoxicity or mutagenicity was observed when /sup 131/IdUrd in the cells was not incorporated into DNA. These preliminary results suggest that, unlike /sup 3/H-Thymidine, the biological effects of the two radioiodine-labeled nucleotide precursors may result largely from a transmutation/fragmentation effect. On the other hand, a low though significant frequency of transformation was associated with cell membrane exposure from /sup 125/I-labeled sodium iodide. 11 refs., 6 figs., 1 tab.
Research Organization:
Harvard Univ., Boston, MA (USA). School of Public Health
DOE Contract Number:
AC02-77EV04322
OSTI ID:
6935408
Report Number(s):
DOE/EV/04322-T4; ON: DE87008017
Country of Publication:
United States
Language:
English