Abstract
Flow cytometric analysis of the cellular DNA content and high pressure liquid chromatographic analysis of the cellular concentration of the polyamines putrescine, spermidine and spermine have been performed on exponentially growing populations of rat brain tumor cells following treatment with methylglyoxal-bis(guanylhydrazone) (MeGAG). This drug has previously been found to be a potent inhibitor of S-adenosyl-l-methionine decarboxylase, the enzyme that catalyzes the initial step in spermidine and spermine biosynthesis. MeGAG was found to inhibit cell proliferation within one generation time. During this time it produced an increase in the fraction of cells with a 2C DNA content (cells in the G1 phase of the cell cycle). Continued accumulation of cells in the G1 phase occurred with sustained treatment. Drug treatment also resulted in a marked decrease in the cellular spermidine and spermine concentraions. Cells did not emerge from their G1-arrest after the addition of spermidine or fresh medium and apparently had become irreversibly blocked by the drug. We suggest that (1) growth inhibition by MeGAG was due to depletion of the cellular pools of spermidine and spermine, and that (2) the cells accumulated in the G1 phase of the cell cycle because of a possible requirement for spermidine and spermine during the subsequent phases (S, G2 and M), the period during which polyamine biosynthesis and accumulation take place in continuously dividing mammalian cells.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1009-1017 |
| Number of pages | 9 |
| Journal | European Journal of Cancer (1965) |
| Volume | 13 |
| Issue number | 9 |
| DOIs | |
| State | Published - 1977 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Oncology
Cite this
Effect of methylglyoxal-bis (guanylhydrazone), an inhibitor of spermidine and spermine synthesis, on cell cycle traverse. / Heby, Olle; Marton, Laurence J.; Wilson, Charles B.; Gray, Joe.
In: European Journal of Cancer (1965), Vol. 13, No. 9, 1977, p. 1009-1017.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Effect of methylglyoxal-bis (guanylhydrazone), an inhibitor of spermidine and spermine synthesis, on cell cycle traverse
AU - Heby, Olle
AU - Marton, Laurence J.
AU - Wilson, Charles B.
AU - Gray, Joe
PY - 1977
Y1 - 1977
N2 - Flow cytometric analysis of the cellular DNA content and high pressure liquid chromatographic analysis of the cellular concentration of the polyamines putrescine, spermidine and spermine have been performed on exponentially growing populations of rat brain tumor cells following treatment with methylglyoxal-bis(guanylhydrazone) (MeGAG). This drug has previously been found to be a potent inhibitor of S-adenosyl-l-methionine decarboxylase, the enzyme that catalyzes the initial step in spermidine and spermine biosynthesis. MeGAG was found to inhibit cell proliferation within one generation time. During this time it produced an increase in the fraction of cells with a 2C DNA content (cells in the G1 phase of the cell cycle). Continued accumulation of cells in the G1 phase occurred with sustained treatment. Drug treatment also resulted in a marked decrease in the cellular spermidine and spermine concentraions. Cells did not emerge from their G1-arrest after the addition of spermidine or fresh medium and apparently had become irreversibly blocked by the drug. We suggest that (1) growth inhibition by MeGAG was due to depletion of the cellular pools of spermidine and spermine, and that (2) the cells accumulated in the G1 phase of the cell cycle because of a possible requirement for spermidine and spermine during the subsequent phases (S, G2 and M), the period during which polyamine biosynthesis and accumulation take place in continuously dividing mammalian cells.
AB - Flow cytometric analysis of the cellular DNA content and high pressure liquid chromatographic analysis of the cellular concentration of the polyamines putrescine, spermidine and spermine have been performed on exponentially growing populations of rat brain tumor cells following treatment with methylglyoxal-bis(guanylhydrazone) (MeGAG). This drug has previously been found to be a potent inhibitor of S-adenosyl-l-methionine decarboxylase, the enzyme that catalyzes the initial step in spermidine and spermine biosynthesis. MeGAG was found to inhibit cell proliferation within one generation time. During this time it produced an increase in the fraction of cells with a 2C DNA content (cells in the G1 phase of the cell cycle). Continued accumulation of cells in the G1 phase occurred with sustained treatment. Drug treatment also resulted in a marked decrease in the cellular spermidine and spermine concentraions. Cells did not emerge from their G1-arrest after the addition of spermidine or fresh medium and apparently had become irreversibly blocked by the drug. We suggest that (1) growth inhibition by MeGAG was due to depletion of the cellular pools of spermidine and spermine, and that (2) the cells accumulated in the G1 phase of the cell cycle because of a possible requirement for spermidine and spermine during the subsequent phases (S, G2 and M), the period during which polyamine biosynthesis and accumulation take place in continuously dividing mammalian cells.
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UR - http://www.scopus.com/inward/citedby.url?scp=0017671666&partnerID=8YFLogxK
U2 - 10.1016/0014-2964(77)90180-3
DO - 10.1016/0014-2964(77)90180-3
M3 - Article
VL - 13
SP - 1009
EP - 1017
JO - European journal of cancer
JF - European journal of cancer
SN - 0014-2964
IS - 9
ER -