Radiation survival properties of cultured human gastric adenocarcinoma cells and the effect of AT-1727

Journal Article · Wed Feb 01 04:00:00 EST 1989 · Int. J. Radiat. Oncol., Biol. Phys.; (United States)

OSTI ID:6324659

He, S Q; Li, C F; Zhen, X Y; Zhou, J; Liu, T F

Tumor cells (SGC-7901) obtained from a human gastric adenocarcinoma have been examined with regard to their intrinsic sensitivity to gamma-irradiation and as to how this intrinsic sensitivity might be altered by growth in a synthesized agent AT-1727 (N4-morpholino-methyl-3,5-dioxopiperazynyl-1,2 ethanl). Clonogenic survival was measured via colony formation assays and fitted to single-hit-multitarget formula. Exponentially growing cells exhibited the mean of survival parameters: D0 = 0.86 + 0.04 Gy; n = 7.03 + 2.3; Dq = 1.63 + 0.23 Gy and SF2 (surviving fraction of conventional daily clinical dose of 2 Gy) = 45-50%. Split-dose survival assays and delayed plating methods were used to exploit the capacity of sublethal damage repair of this cell line studied demonstrating the reappearance of initial shoulder on the survival curve and an increased survival. Alteration of radiosensitivity of SGC cells by AT-1727 was shown when cultures were incubated in a medium with the drug for a 6 hr interval between split dose irradiation, indicating the inhibition of sublethal damage repair. The radioresistance of hypoxic SGC cells was decreased when pre-treatment with AT-1727 was given 2 hr before irradiation, and the decrease of surviving fraction was drug-dose dependent. A maximum enhanced effect was obtained when 0.15 mM of AT-1727 was used, reaching an ER of 1.24. Inhibition of sublethal damage repair and action as a hypoxic radiosensitizer were considered to be two parts of the mechanism of AT-1727 in modification of radiation effects.

• Research Organization: Shanghai Medical Univ. (China)
• OSTI ID: 6324659
• Journal Information: Int. J. Radiat. Oncol., Biol. Phys.; (United States), Journal Name: Int. J. Radiat. Oncol., Biol. Phys.; (United States) Vol. 16:2; ISSN IOBPD
• Country of Publication: United States
• Language: English

Related Subjects

560120* -- Radiation Effects on Biochemicals
Cells
& Tissue Culture
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
AZINES
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
CARCINOMAS
COLONY FORMATION
DISEASES
DNA REPAIR
DRUGS
ELECTROMAGNETIC RADIATION
EVALUATION
GAMMA RADIATION
HETEROCYCLIC COMPOUNDS
IN VITRO
IONIZING RADIATIONS
NEOPLASMS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PIPERAZINES
PYRAZINES
RADIATIONS
RADIOSENSITIVITY
RADIOSENSITIVITY EFFECTS
RADIOSENSITIZERS
RECOVERY
REPAIR
SURVIVAL CURVES
TUMOR CELLS