Enhanced malignant transformation is accompanied by increased survival recovery after ionizing radiation in Chinese hamster embryo fibroblasts
- Univ. of Wisconsin, Madison, WI (United States)
Transformed Chinese hamster embryo fibroblasts (CHEF), which gradually increase in tumor-forming ability in nude mice, were isolated from normal diploid CHEF/18 cells. Transformed CHEF cells (i.e., T30-4 > 21-2M3 > 21-2 > normal CHEF/18) showed gradual increases in potentially lethal damage (PLD) survival recovery. {beta}-Lapachone and camptothecin, modulators of topoisomerase I (Topo I) activity, not only prevented survival recovery in normal as well as in tumor cells, but enhanced unscheduled DNA synthesis. These seemingly conflicting results are due to the fact that Topo I activity can be modulated by inhibitors to convert single-stranded DNA lesions into double-stranded breaks. Increases in unscheduled DNA synthesis may result from a continual supply of free ends, on which DNA repair processes may act. Altering Topo I activity with modulators appears to increase X-ray lethality via a DNA lesion modification suicide pathway. Cells down-regulate Topo I immediately after ionizing radiation to prevent Topo I-mediated lesion modification and to enhance survival recovery. 16 refs., 3 figs., 1 tab.
- Sponsoring Organization:
- USDOE
- OSTI ID:
- 56783
- Report Number(s):
- CONF-9305202--; CNN: Grant PDT-431/DHP-90A
- Journal Information:
- Radiation Research, Journal Name: Radiation Research Journal Issue: 1 Vol. 138; ISSN 0033-7587; ISSN RAREAE
- Country of Publication:
- United States
- Language:
- English
Similar Records
Inhibition of radiation-induced neoplastic transformation by. beta. -lapachone
Additive and supraadditive interaction between ionizing radiation and pazelliptine, a DNA topoisomerase inhibitor, in Chinese hamster V-79 fibroblasts
Involvement of DNA topoisomerase I in transcription of human ribosomal RNA genes
Journal Article
·
Sat Jul 01 00:00:00 EDT 1989
· Proceedings of the National Academy of Sciences of the United States of America; (USA)
·
OSTI ID:5297005
Additive and supraadditive interaction between ionizing radiation and pazelliptine, a DNA topoisomerase inhibitor, in Chinese hamster V-79 fibroblasts
Journal Article
·
Sat Jun 15 00:00:00 EDT 1991
· Cancer Research; (United States)
·
OSTI ID:5592577
Involvement of DNA topoisomerase I in transcription of human ribosomal RNA genes
Journal Article
·
Sun Jan 31 23:00:00 EST 1988
· Proc. Natl. Acad. Sci. U.S.A.; (United States)
·
OSTI ID:6879289