Cytotoxic effect in vivo of selected chemotherapeutic agents on synchronized murine fibrosarcoma cells

Grdina, David J.; Sigdestad, Curtis P.; Peters, Lester J.

doi:10.1038/bjc.1980.301

Cited by 18 publications

(14 citation statements)

References 12 publications

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“…Other workers using c-DDP on cells both in vitro (Meyn et al 1980, Roberts andFraval 1980) and in vivo (Grdina et al 1980), have demonstrated greatest sensitivity to the drug in G1 and least sensitivity in S, i.e. similar to X-rays.…”

Section: Radiosensitization By Cisplatinmentioning

confidence: 97%

Radiosensitization by Cisplatin of RIF1 Tumour Cellsin Vitro

Begg

Kolk

Dewit

et al. 1986

International Journal of Radiation Biology and Related Studies

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The ability of cis-diamminedichloroplatinum (II) (c-DDP) to enhance radiation-induced cell killing was tested on oxic RIF1 tumour cells in monolayer culture. Marked radiosensitization of the survivors of a 1 h drug treatment was found with all c-DDP doses tested, with enhancement ratios increasing from 1.2 to 2.2 with increasing drug dose. Isobologram analyses showed that the interactions of c-DDP with X-rays were supra-additive. To test whether part of the enhancement was due to a selection of subpopulations, the diploid and tetraploid RIF1 cells, which normally coexist in culture, were separated by unit gravity velocity sedimentation, and by developing diploid and tetraploid clones. Both methods showed that there was little difference in either drug sensitivity or radiation sensitivity between diploid and tetraploid cells. DNA histograms obtained by flow cytometry showed little or no cycle progression during the 1 h drug treatment. These data indicate that the radiosensitization was not the result of the drug exposure leaving cells in a radiosensitive phase. The observed radiosensitization, therefore, appears to have resulted from a true drug/X-ray interaction.

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Section: Radiosensitization By Cisplatinmentioning

confidence: 97%

Radiosensitization by Cisplatin of RIF1 Tumour Cellsin Vitro

Begg

Kolk

Dewit

et al. 1986

International Journal of Radiation Biology and Related Studies

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“…In an excellent review in which the varying results of BLM in CHO, Hela, and human lymphoma cells by a number of authors are discussed, Twentyman [20] concludes that it is difficult to arrive at any generally-useful conclusions regarding the cell cycle phase specificity of BLM. There appears to be general agreement on the mitotic sensitivity being the greatest for BLM, but little other agreement for the other cell phases [1,20,21]. A more useful generalization for cell cycle age response is found for ADR.…”

mentioning

confidence: 90%

Comparison of cancer chemotherapeutic agents in asynchronous and synchronous 9L cells

1987

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The cytotoxic activity of various chemotherapy agents was investigated in asynchronous populations of cultured 9L rat brain tumor cells, and as a function of their position in the cell cycle. Representative drugs from the classes of DNA-active agents, alkylating agents, spindle poisons, and antimetabolites were tested. The ability to induce cell lethality in asynchronous populations as a function of drug concentration varied for 1 hr pulse exposures. In order of decreasing cytotoxic activity, DHAQ was the most effective, followed by VCR, VDS, VBL, ADR, BCNU, cis-DDP, BLM, DBD, RZ, and HU. The effect of chemotherapy agents on synchronous 9L cells obtained by mitotic selection also varied with respect to the individual agent and was cell cycle-dependent. Survival age-responses ranged from being minimal to demonstrating significant fluctuations as a function of cell cycle position. For all agents except ADR and HU, the sensitivity of G1 phase was greater than S phase. RZ exhibited essentially a flat age-response. Comparison of the cell cycle age-responses of chemotherapeutic agents to those exhibited by the cytotoxic modalities of radiation and hyperthermia demonstrate several unique differences.

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“…Recently, a simple in vivo procedure has been developed and described for characterizing the phase-specific therapeutic effectiveness of selected cytotoxic agents [6,11,12]. This procedure entails the i.v.…”

Section: Introductionmentioning

confidence: 99%

Treatment of artificially-induced pulmonary metastases with fractionated doses of vincristine and/or radiation therapy

Grdina

White

1983

Clin Exp Metast

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The cytotoxic effects in vivo of vincristine (VC), radiation, or both modalities in combination on murine fibrosarcoma (FSa) cells grown as pulmonary tumors were determined. Fourteen days following the i.v. injection of viable FSa cells, recipient mice developed between 100 and 150 visible pulmonary nodules. At that time, tumor-bearing animals were exposed to either single or combined modality treatments, as well as single and fractionated dose regimens. Animals were sacrificed 1 hour after the last treatment. Tumor nodules were excised and made into a single cell suspension and separated on the basis of cell size by centrifugal elutriation. Flow microfluorometry (FMF) was used to determine the cell-cycle parameters and the relative synchrony of the separated populations, as well as the percentage contamination by normal diploid cells in each of the tumor cell populations. Known numbers of viable cells from each elutriator fraction were injected into recipient mice to determine their colony-forming efficiency (CFE). Surviving fractions were determined by comparing the CFEs of treated FSa cells from each of the separated elutriator fractions with those of appropriate untreated controls. Following a single dose of VC (1 mg/kg), populations of cells enriched in late S and G2 + M were the most sensitive. However, following the administration of five doses (0.25 mg/kg each) over a 24 hour period, populations of cells most enriched in G1 cells exhibited the lowest percentage of survivors. A single dose of radiation (1000 rad) was most effective in killing S-phase cells. When administered in five fractions (250 rad per fraction), each separated by a 6 hour interval, no phase-specific sensitivity was observed. The combination of both modalities exhibited a marked schedule dependence, with a single dose (1000 rad) of radiation followed by five doses of VC (0.25 mg/kg) being the most effective treatment protocol observed.

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Cytotoxic effect in vivo of selected chemotherapeutic agents on synchronized murine fibrosarcoma cells

Cited by 18 publications

References 12 publications

Radiosensitization by Cisplatin of RIF1 Tumour Cellsin Vitro

Radiosensitization by Cisplatin of RIF1 Tumour Cellsin Vitro

Comparison of cancer chemotherapeutic agents in asynchronous and synchronous 9L cells

Treatment of artificially-induced pulmonary metastases with fractionated doses of vincristine and/or radiation therapy

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