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Heterogeneous survival responses of human gastric cancer clones to αDifluoromethylornithine in vitro

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Abstract

The effects of αDifluoromethylornithine (DFMO)2 on survival of human gastric cancer clones were studied in vitro. The responses were dose and time dependent. Treatments which lasted for less than 12 h were cytotoxic at only the highest doses used. The greatest effects on survival were observed only when cells were treated for 48 and 72 h. The effects on the clones produced by such prolonged treatment durations were heterogeneous, with survival values differing by as much as 460%. By contrast, the clonal survival responses to short DFMO treatments (12 h) were very uniform (dose differential of only 19%); however, this uniformity in response could be achieved only by using non-pharmacological doses of DFMO. The heterogeneity in survival responses in the clones might be slightly associated with their levels of intracellular spermidine. Clones with the smallest amounts of intracellular spermidine at the start of treatment were most sensitive to DFMO. However, this association may not hold up with further testing in other gastric cancer clones or when studied in other cancer lines in vitro.

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Abbreviations

LD90 :

dose lethal to 90% of the cell population

D0 :

dose required to reduce survival by 63% on exponential portion of the survival curve

MeCCNU:

1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea

Bleo:

Bleomycin

5FU:

5 fluorouracil

DFMO:

αDifluoromethylornithine

ODC:

ornithine decarboxylase

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Authors and Affiliations

  1. Department of Radiation Therapy, Eastern Virginia Medical School, 23507, Norfolk, Virginia, USA

    S. C. Barranco Ph.D.

  2. Division of Research, University of Texas Medical Branch, Walls Medical Research Foundation, 310 Gail Borden Building D11, 77550, Galveston, Texas, USA

    P. J. Ford

  3. Department of Surgery, Division of Research, University of Texas Medical Branch, 310 Gail Borden Building D11, 77550, Galveston, Texas, USA

    C. M. Townsend Jr

Authors
  1. S. C. Barranco Ph.D.
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  2. P. J. Ford
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  3. C. M. Townsend Jr
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Barranco, S.C., Ford, P.J. & Townsend, C.M. Heterogeneous survival responses of human gastric cancer clones to αDifluoromethylornithine in vitro. Invest New Drugs 4, 337–345 (1986). https://doi.org/10.1007/BF00173506

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