The Relevance of Cell Kinetics in Determining Drug Activity in vitro

Drewinko, Benjamin; Barlogie, Barthel

doi:10.1007/978-1-4684-4046-1_35

Cited by 4 publications

(8 citation statements)

References 34 publications

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“…As extensively discussed by Drewinko and Barlogie [1], extrapolation of results obtained on a given cell line to a generalized statement applicable to the response of all mammalian cells is often inadequate. This is a result of differences in synchrony TIne after incubation, hours…”

Section: Discussionmentioning

confidence: 99%

“…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: 89%

“…In the evaluation of new drugs for their potential utilization as chemotherapeutic agents, determination of relative cytotoxic activities as well as the kinetics of cell killing is valuable [1]. Cytokinetic data obtained in cell cycle analysis may indicate dose and time manipulations of clinical scheduling for different combinations of drugs given simultaneously or in sequence.…”

Section: Introductionmentioning

confidence: 99%

“…Considering combination treatments, agents with different phase sensitivities could be paired in an attempt to achieve significant killing of all cells composing a tumor population. Attempts are being made to combine cytokinetic data with the knowledge of age-dependent responses so as to provide new approaches to combination therapy, e.g, accumulating a large population of cells in a specific cell cycle stage and then utilizing a second drug (or drug combination) for which the main killing effect is in that phase [ 1,2]. For these reasons, evaluation of chemotherapeutic agents should include studies not only in asynchronous but also synchronous populations of cells.…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

1987

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“…For relevant comparisons of the sensitivity to DNA-damaging agents among strains derived from different donors, it is important to match the growth state of cells, because the degree of cytotoxicity induced by chemical compounds differs, depending on the state of proliferation of the cells (Drewinko and Barlogie, 1982). We found that the survival curves of a cell strain varied at different states of proliferation after exposure to MNNG, MMC, or 4NQO, whereas there was no varia-tion after exposure to EMS (Fig.…”

Section: Discussionmentioning

confidence: 99%

Patients with tuberous sclerosis have fibroblasts with normal limits for growth characteristics and sensitivities to DNA alkylating agents

Ohno

Takeshita

1984

Jap J Human Genet

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SummaryTuberous sclerosis (TS) is an autosomal dominant neurocutaneous syndrome characterized by hamartomatous growth in multisystems. To determine the gene expression in cultured fibroblasts, we studied several in vitro properties of skin fibroblasts. Measurements of the attachment ratio, the colony-forming efficiency, the population doubling time, and the saturation density in 10~ fetal bovine serum show that fibroblasts from five TS patients proliferate in the same manner as do the age-matched controls. We also measured the survival of TS fibroblasts after treatment with a variety of chemical agents. TS fibroblasts are equal to controls in their sensitivity to four types of alkylating agents including N-methyl-N'-nitro-N-nitrosoguanidine to which TS fibroblasts have been reported to be hypersensitive. These results suggest that the in vitro properties of TS fibrobtasts do not resemble cells from patients with several autosomal recessive disorders predisposing to neoplasms and displaying hypersensitivity to DNA damages.

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