Treatment of cells with the polyamine analog N, N11-diethylnorspermine retards S phase progression within one cell cycle.
When Chinese hamster ovary cells were seeded in the presence of the spermine analog N1,N11-diethylnorspermine (DENSPM), cell proliferation ceased; this was clearly apparent by cell counting 2 days after seeding the cells. However, 1 day after seeding there was a slight difference in cell number between control and DENSPM-treated cultures. To investigate the reason for this easily surpassed slight difference, we used a sensitive bromodeoxyuridine/flow cytometry method. Cell cycle kinetics were studied during the first cell cycle after seeding cells in the absence or presence of DENSPM. Our results show that DENSPM treatment did not affect the progression of the cells through G1 or the first G1/S transition that took place after seeding the cells. The first cell cycle effect was a delay in S phase as shown by an increase in the DNA synthesis time. The following G2/M transition was not affected by DENSPM treatment. DENSPM treatment inhibited the transient increases in putrescine, spermidine, and spermine pools that took place within 24 h after seeding. Thus, in conclusion, the first cell cycle phase affected by the inhibition of polyamine biosynthesis caused by DENSPM was the S phase. Prolongation of the other cell cycle phases occurred at later time points, and the G1 phase was affected before the G2/M phase.
Alm
K
K
Department of Animal Physiology, Lund University, Sweden; Roswell Park Cancer Institute, Grace Cancer Drug Center, Buffalo, New York, USA. Kersti.Alm@zoofys.lu.se
Berntsson
P S
PS
Kramer
D L
DL
Porter
C W
CW
Oredsson
S M
SM
D000578:Amidines / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015317:Biogenic Polyamines / Q000032:analysis; D001973:Bromodeoxyuridine / Q000378:metabolism; D016466:CHO Cells; D006224:Cricetinae; D004247:DNA / Q000032:analysis; D016193:G1 Phase / Q000187:drug effects; D007189:Indans / Q000494:pharmacology; D016196:S Phase / Q000187:drug effects*; D013096:Spermine / Q000031:analogs & derivatives* / Q000494:pharmacology
D000578:Amidines; D000970:Antineoplastic Agents; D015317:Biogenic Polyamines; D007189:Indans; C059685:N(1),N(11)-diethylnorspermine; C082408:4-amidinoindan-1-one 2'-amidinohydrazone; D013096:Spermine; D004247:DNA; D001973:Bromodeoxyuridine