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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Investigational new drugs 4 (1986), S. 337-345 
    ISSN: 1573-0646
    Keywords: heterogeneity ; polyamines ; cell killing
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: 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.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1573-0646
    Keywords: heterogeneity ; polyamines ; cell killing ; kinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The effects of α-difluoromethylornithine (DFMO) on survival, cell kinetics and polyamine levels were studied on two clones of human astrocytoma in vitro. The survival responses were dose and time dependent; and treatments with DFMO which lasted for 72 h resulted in heterogeneous responses with one clone being up to 6 times more sensitive than the other. Shorter treatments produced more uniform killing in the clones. A continuous exposure of the cells to 5 mM DFMO resulted in a rapid decrease in putrescine values in both clones, followed by decreases in the spermidine levels. These effects were closely followed by 148% to 170% increases in cell population doubling times, and a lowering of saturation densities. No clear correlations could be established among baseline polyamine levels and cell kinetics or survival responses to DFMO treatments.
    Type of Medium: Electronic Resource
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