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-; ISSN 0033-7587; CNN: Grant PDT-431/DHP-90A; TRN: 95:012962
- Journal Information:
- Radiation Research, Vol. 138, Issue 1; Conference: Molecular, cellular, and genetic basis of radiosensitivity at low doses: a case of induced repair, Whistler (Canada), 9-13 May 1993; Other Information: PBD: Apr 1994
- Country of Publication:
- United States
- Language:
- English
Similar Records
Role of x-ray-induced transcripts in adaptive responses following x-rays
Role of x-ray-induced transcripts in adaptive responses following x-rays. Progress report, year 1