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K T Wheeler

Publications and source records attributed to K T Wheeler.

At least 91 records · Page 5Linked to original sources
PubMed1975

Cellular radiosensitivity of a rat brain tumor.

The response of a model brain tumor system in the rat to single doses of x irradiation has been studied. Solid tumors were exposed in situ, removed, dissociated into single cells, and grown in tissue culture. The fraciton of surviving clonogenic cells wasdetermined as a function of x-ray dose level for tumors irradiated in anesthetized, air-breathing rats, and for tumors irradiated in rats killed 5 minutes prior to irradiation bynitrogen gas asphyxiation. The parameters of the survival curve for tumors irradiatedin air-breathing rats were: DO= 295 rads; DQ= 350 rads; and n= 3.0. Similarly, thesurvival parameters for tumors irradiated in nitrogen gas asphyxiated rats were: DO=625 rads; DQ=675 rads; and n= 3.0. The survival curve of these tumor cells when assayed in in vitro tissue culture only has parameters of: DO= 225 rads; DQ= 350 rads; andn= 4.7. Data form the in vivo to in vivo tumor cell survival curves suggest that there is no significant hypoxic fraction in this brain tumor.

Animals↗
PubMed1975

Chemotherapeutic implications of early tumor cell growth in an animal brain-tumor model.

The onset of tumor cell proliferation was determined in an animal brain-tumor model in which tumor cells had been injected into the cerebrum of rats through a hollow stainless steel screw implanted stereotactically. Tritiated thymidine uptake in the DNA at various periods after injection of tumor cells indicated no significant proliferation of tumor cells until 168-192 hours post implantation, after which tritium uptake increased exponentially. Control rats with screws alone or screws through which balanced salt solution had been injected showed an increased uptake at 72 hours, a phenomenon not observed in animals given tumor cells. Our findings suggested that, in the tumor model described, experimental chemotherapy tests should be deferred until at least 7 days post implantation.

Animals↗
PubMed1975

In vitro evaluation of in vivo brain tumor chemotherapy with 1,3-bis(2-chloroethyl)-1-nitrosourea.

An in vitro colony formation assay was used to determine the efficacy of in vitro therapy with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) on a rat brain tumor. The fraction of clonogenic cells surviving in vivo therapy was determined by a comparison between the in vitro colony-forming capacity of cells derived from previously treated and untreated tumors. With this intracerebral solid tumor a direct correlation was found between the surviving fraction of cells and animal survival, implying that the in vitro assay system is a reliable test of therapeutic effect. The BCNU dose-response curve was exponential up to a dose of 0.75 times the LD10 dose with little additional cell kill noted at higher drug levels. This plateau does not appear to represent a resistant subpopulation of cells, since retreatment of tumors derived from cells surviving an LD10 dose were as sensitive to BCNU as those with no prior drug exposure. Instead, it may represent, at least in part, failure of the drug to reach and/or enter cells in all parts of solid tumors. On the average BCNU doses of 0.75 times the LD10 dose or greater resulted in slightly more than a 3-log cell kill and doubled the life-span for our tumor-bearing animals. The finding that an increase in animal life-span requires at least a 1-log tumor cell kill indicates that survival studies with intracranial tumor models may be insensitive to single courses of many chemotherapeutic agents with modest but significant antitumor activity.

Animals↗
PubMed1975

Factors influencing the survival of rat brain tumor cells after in vitro treatment with 1,3-bis(2-chloroethyl)-1-nitrosourea.

The shape of dose-response curves obtained for asynchronous, exponentially growing 9L rat brain tumor cells treated in vitro with 1,3-bis(2-chloroethyl)-1-nitrosourea changed as a function of the drug exposure time. For short treatment times (less than 1 hr), the dose-response curves had shoulders, indicating that the cells may accumulate sublethal damage; however, after longer treatments (greater than 1 hr), little if any shoulder was apparent. The slope of the exponential portion of the dose-response curve increased progressively with treatment periods from 15 min to 2 hr. Longer exposure times (up to 24 hr) produced no further changes in the cell-kill kinetics. Cell survival was directly related to the BCNU exposure dose [o integral t Co(t)dt] and to the amount of bound BCNU per cell. Extrapolation of the curves for these two variables indicated that some BCNU damage accumulates before death occurs. The amount of serum and cell products available in the medium to bind BCNU affected the level of survival; however, there was no evidence that extracellular spontaneous breakdown products or chemical transformation products were involved in the cell-killing mechanism.

Animals↗
PubMed1974

On the possibility that DNA repair is related to age in non-dividing cells.

Possible age-related deterioration in the efficacy of DNA repair was investigated in a complement of non-dividing mammalian cells which is not replenished during the lifetime of the animal. Internal granular-layer neurons were extracted from the cerebella of beagle dogs, aged from 7 weeks to 13 years, following exposure in situ to 4700 rads of collimated (60)Co gamma rays. The alkaline sucrose-gradient sedimentation profiles obtained from the DNA of those neurons after various post-irradiation periods in situ can be interpreted: (a) that there is not an age-associated decrease in the ability of the cells to rejoin the single-strand breaks induced by radiation, but (b) that there may be an age-associated decline in the size of the DNA-containing species which can be extracted from unirradiated cells. The latter effect may reflect normal aging of the cerebellum.

Aging↗