Correlation between the effects of polyamine analogues on DNA conformation and cell growth.
Effects of a number of synthetic analogues of the natural polyamines on the B-Z transition of poly(dG-me5dC) and on the aggregation of calf thymus DNA in solution were studied using circular dichroic and UV spectroscopy. The efficiency of induction of the B-Z transition decreased with a decrease in the length of the central alkyl chain of the analogues, and the ability of analogues to aggregate DNA was markedly reduced for compounds ethylated at the terminal amines. Both structural variations appear to have important effects on the biological functions of polyamines. Most analogues studied depleted intracellular levels of natural polyamines, but only those that did not readily induce the B-Z transition and/or aggregate DNA were good inhibitors of cell growth. All but one of the analogues studied were able to rescue cells--at least in part--from the growth-inhibitory effects of alpha-difluoromethylornithine. The single analogue that was unable to effect rescue also failed to induce both the B-Z transition and the aggregation of DNA.
Basu
H S
HS
Brain Tumor Research Center, Department of Neurological Surgery, School of Medicine, University of California, San Francisco 94143.
Feuerstein
B G
BG
Deen
D F
DF
Lubich
W P
WP
Bergeron
R J
RJ
Samejima
K
K
Marton
L J
LJ
D000818:Animals; D002455:Cell Division / Q000187:drug effects*; D002942:Circular Dichroism; D004247:DNA / Q000187:drug effects / Q000648:ultrastructure*; D000518:Eflornithine / Q000494:pharmacology; D009690:Nucleic Acid Conformation / Q000187:drug effects*; D011073:Polyamines / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D013056:Spectrophotometry, Ultraviolet; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D011073:Polyamines; D004247:DNA; D000518:Eflornithine