The effects of altered fractionation schedules on the survival of human cell lines differing in their proliferative activity and repair capacity

Journal Article · Wed Nov 01 04:00:00 EST 1989 · International Journal of Radiation Oncology, Biology and Physics; (USA)

DOI:https://doi.org/10.1016/0360-3016(89)90148-X· OSTI ID:5099571

Konefal, J B; Taylor, Y C ^[1]

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1. Washington Univ. School of Medicine, St. Louis, MO (USA)

Plateau phase cultures of human cell lines were used as model systems to study the relative influences of proliferation and repair on the effectiveness of altered fractionation schedules. A human normal diploid fibroblast cell line (AG1522) which has a high capacity to repair potentially lethal radiation damage (PLD) and very little proliferative activity when grown to confluence was compared to human tumor cell lines which maintain significant cell-cycle activity in plateau phase. The human fibrosarcoma cell line, HT1080, used in the present study exhibited a much greater rate of turnover than the normal fibroblasts as determined from tritiated thymidine incorporation (5 day labeling index of 66% vs 20%) and no PLD repair, as determined by delayed plating experiments, in plateau phase. Twenty Gy were delivered to both cell lines over 5 days in 3 regimens: one 4 Gy fraction/day, two 2 Gy fractions/day with a 2 hr interval between doses, and two 2 Gy fractions/day with a 6 hr interval between doses. Although the normal fibroblasts demonstrated the greatest sparing between acute single doses and one 4 Gy fraction/day, there was little additional benefit (increased survival) from the increased dose fractionation. In contrast, the twice daily fractionation schedules resulted in significant differential sparing of the fibrosarcoma cells compared to the normal fibroblasts. With the 6 hr interval between doses, the survival advantages of the cell line with the slow turnover rate and high PLD repair capacity were completely lost. Split-dose experiments indicated slightly less sublethal damage repair in the fibrosarcoma cell line, but for both cell lines recovery was complete in 2 hr. DNA distributions were measured by flow cytometry and long term labeling index measurements performed in parallel with the multifraction radiation survival studies.

• OSTI ID: 5099571
• Journal Information: International Journal of Radiation Oncology, Biology and Physics; (USA), Journal Name: International Journal of Radiation Oncology, Biology and Physics; (USA) Vol. 17:5; ISSN IOBPD; ISSN 0360-3016
• Country of Publication: United States
• Language: English

Related Subjects

550901 -- Pathology-- Tracer Techniques
560120* -- Radiation Effects on Biochemicals
Cells
& Tissue Culture
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
ANIMALS
AZINES
BIOLOGICAL EFFECTS
BIOLOGICAL RADIATION EFFECTS
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
CELL CULTURES
CELL CYCLE
CELL FLOW SYSTEMS
CELL PROLIFERATION
CONNECTIVE TISSUE CELLS
DIPLOIDY
DNA REPAIR
DOSES
FIBROBLASTS
FRACTIONATED IRRADIATION
HETEROCYCLIC COMPOUNDS
HYDROGEN COMPOUNDS
IRRADIATION
ISOTOPE APPLICATIONS
MAMMALS
MAN
NUCLEOSIDES
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PLOIDY
PRIMATES
PYRIMIDINES
RADIATION DOSES
RADIATION EFFECTS
RECOVERY
REPAIR
RIBOSIDES
SOMATIC CELLS
SURVIVAL CURVES
THYMIDINE
TRACER TECHNIQUES
TRITIUM COMPOUNDS
TUMOR CELLS
VERTEBRATES