Effects of cis-diamminedichloroplatinum (II) and radiation on the proliferation kinetics of mouse duodenal crypt cells and on a partially synchronized crypt cell population

Journal Article · Fri Oct 31 23:00:00 EST 1986 · Int. J. Radiat. Oncol., Biol. Phys.; (United States)

DOI:https://doi.org/10.1016/0360-3016(86)90135-5· OSTI ID:6847465

Dewit, L; Oussoren, Y; Bartelink, H

The effects of c-DDP and radiation, given alone or in combination, on the proliferation kinetics of mouse duodenal crypt cells were investigated by repeated labelling with /sup 3/H-thymidine. Crypt cells surviving a single dose of X-rays or c-DDP alone, appeared to proliferate faster than untreated controls. When both agents were given in combination, the proliferation rate of surviving crypt cells was markedly reduced as a result of a significant increase in the DNA synthesis time. The influence of the proliferation rate of crypt cells on the effects of c-DDP and X rays was analyzed using the crypt microcolony assay. Mice were given single doses or 2 fractions of X rays with 2 different time intervals (4 and 48 hours) either alone or in combination with c-DDP given 30 minutes before the second fraction. The lethal effect of the drug was approximately the same in cells that were in accelerated proliferation after the first irradiation as in unstimulated cells. A tendency for less cell killing by the drug was observed 3.5 hours after the first irradiation. To rule out cell age dependent effects of c-DDP, crypt cell survival was assessed after irradiation was given alone or in combination with the drug on a partially synchronized crypt cell population, obtained by repeated injections of hydroxyurea. A predominant lethal effect of c-DDP was found in cells in the late G1-phase. These findings are important to consider both from a mechanistic point of view as for clinical application of the agents.

• Research Organization: Netherlands Cancer Institute, Amsterdam
• OSTI ID: 6847465
• Journal Information: Int. J. Radiat. Oncol., Biol. Phys.; (United States), Journal Name: Int. J. Radiat. Oncol., Biol. Phys.; (United States) Vol. 11; ISSN IOBPD
• Country of Publication: United States
• Language: English

Related Subjects

560120* -- Radiation Effects on Biochemicals
Cells
& Tissue Culture
560300 -- Chemicals Metabolism & Toxicology
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
AMIDES
ANIMAL CELLS
ANIMALS
AZINES
BIOLOGICAL EFFECTS
BIOLOGICAL RADIATION EFFECTS
CELL CULTURES
CELL DIVISION
CELL KILLING
CELL PROLIFERATION
DNA
ELECTROMAGNETIC RADIATION
ELEMENTS
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
HYDROXYUREA
IONIZING RADIATIONS
LABELLED COMPOUNDS
MAMMALS
METALS
MICE
NUCLEIC ACIDS
NUCLEOSIDES
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PLATINUM
PLATINUM METALS
PYRIMIDINES
RADIATION EFFECTS
RADIATIONS
RIBOSIDES
RODENTS
SOMATIC CELLS
SYNERGISM
THYMIDINE
TRANSITION ELEMENTS
TRITIUM COMPOUNDS
VERTEBRATES
X RADIATION