Role of x-ray-induced transcripts in adaptive responses following x-rays. Progress report, year 1
Potentially lethal damage repair (PLDR) and sublethal damage repair, may be the same manifestations of a series of common enzymatic steps. PLDR, has two distinct phases based upon DNA lesion repair and survival recovery studies. The first phase of PLDR occurs very quickly (t{sub {1/2}}:2--20 mins) to increase the survival of X-irradiated cells by mending the vast array of DNA lesions created by ionizing radiation. The second slower phase of PLDR proceeds much later (i.e., >1--2 hrs) following X-irradiation, during which the remaining double-stranded DNA breaks are completely repaired. This second phase of repair closely corresponds to the restructuring of gross chromosomal damage, and can be partially blocked in some human cells by inhibiting protein synthesis. This slower phase of PLDR correlated with a rapid decline in X-ray-induced transformation of normal cells. The fast component of PLDR may be due to constitutively synthesized DNA ligases, topoisomerases, or polymerases, which act immediately to repair damaged, DNA. In contrast, the slow phase of PLDR in human cells may require the induction of specific genes and gene product`s involved in the repair of potentially lethal or carcinogenic DNA lesions. Induced gene products (i.e., proteins) specifically synthesized in response to physiological doses of ionizing radiation in radioresistant human melanoma (U1-Mel) cells, and in a variety of other human normal and cancer-prone cells, were identified using two-dimensional gel electrophoresis. We identified and partially characterized ten proteins synthesized by U1-Mel cells. The synthesis of eight of these proteins were specifically induced by ionizing radiation and two proteins were repressed Neither heat shock, UV-irradiation, nor bifunctional alkylating agent treatments resulted in the induction of these proteins. The expression of one protein, XIP269, correlated very well with PLDR capacity.
- Research Organization:
- Univ. of Michigan, Ann Arbor, MI (United States)
- Sponsoring Organization:
- USDOE, Washington, DC (United States)
- DOE Contract Number:
- FG02-91ER61256
- OSTI ID:
- 10179508
- Report Number(s):
- DOE/ER/61256-1; ON: DE92040814
- Resource Relation:
- Other Information: PBD: [1992]
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
DNA REPAIR
MOLECULAR BIOLOGY
RADIOBIOLOGY
BIOLOGICAL PATHWAYS
DNA HELICASES
ENZYME INDUCTION
DNA POLYMERASES
ENDONUCLEASES
PROGRESS REPORT
X RADIATION
DNA-CLONING
TWO-DIMENSIONAL ELECTROPHORESIS
BIOLOGICAL ADAPTATION
STRAND BREAKS
TRITIUM COMPOUNDS
AUTORADIOGRAPHY
THYMIDINE
560120
550201
RADIATION EFFECTS ON BIOCHEMICALS, CELLS, AND TISSUE CULTURE
TRACER TECHNIQUES