Biochemical evidence for deficient DNA repair leading to enhanced G2 chromatid radiosensitivity and susceptibility to cancer
Human tumor cells and cells from cancer-prone individuals, compared with those from normal individuals, show a significantly higher incidence of chromatid breaks and gaps seen in metaphase cells immediately after G2 X irradiation. Previous studies with DNA repair-deficient mutants and DNA repair inhibitors strongly indicate that the enhancement results from a G2 deficiency(ies) in DNA repair. We report here biochemical evidence for a DNA repair deficiency that correlates with the cytogenetic studies. In the alkaline elution technique, after a pulse label with radioactive thymidine in the presence of 3-acetylaminobenzamide (a G2-phase blocker) and X irradiation, DNA from tumor or cancer-prone cells elutes more rapidly during the postirradiation period than that from normal cells. These results indicate that the DNA of tumor and cancer-prone cells either repairs more slowly or acquires more breaks than that of normal cells; breaks can accumulate during incomplete or deficient repair processes. The kinetic difference between normal and tumor or cancer-prone cells in DNA strand-break repair reaches a maximum within 2 h, and this maximum corresponds to the kinetic difference in chromatid aberration incidence following X irradiation reported previously. These findings support the concept that cells showing enhanced G2 chromatid radiosensitivity are deficient in DNA repair. The findings could also lead to a biochemical assay for cancer susceptibility.
- Research Organization:
- National Cancer Institute, Bethesda, MD
- OSTI ID:
- 6928395
- Journal Information:
- Radiat. Res.; (United States), Vol. 2
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
TUMOR CELLS
DNA REPAIR
RADIOSENSITIVITY
CHROMATIDS
IN VITRO
NEOPLASMS
X RADIATION
ANIMAL CELLS
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
DISEASES
ELECTROMAGNETIC RADIATION
IONIZING RADIATIONS
RADIATIONS
RECOVERY
REPAIR
560120* - Radiation Effects on Biochemicals
Cells
& Tissue Culture