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Polyamine Depletion with Two Different Polyamine Analogues Causes DNA Damage in Human Breast Cancer Cell Lines.

Johansson, Veronica LU ; Oredsson, Stina LU and Alm, Kersti LU (2008) In DNA and Cell Biology 27(9). p.511-516
Abstract
It is well known that the positively charged polyamines have a DNA-stabilizing function and that polyamine depletion alters chromatin function. We have previously shown that polyamine depletion causes an S phase prolongation, and others have shown that there is an accumulation of Okazaki-like fragments in polyamine-depleted cells. In the present study we have used the comet assay to investigate polyamine depletion-induced DNA strand breaks. Three breast cancer cell lines and one normal-like breast cell line were treated with the polyamine analogue N(1),N(11)-diethylnorspermine or with the polyamine biosynthesis inhibitor 4-amidinoindan-1-one 2'-amidinohydrazone (CGP 48664). The comet assay showed that polyamine depletion resulted in DNA... (More)
It is well known that the positively charged polyamines have a DNA-stabilizing function and that polyamine depletion alters chromatin function. We have previously shown that polyamine depletion causes an S phase prolongation, and others have shown that there is an accumulation of Okazaki-like fragments in polyamine-depleted cells. In the present study we have used the comet assay to investigate polyamine depletion-induced DNA strand breaks. Three breast cancer cell lines and one normal-like breast cell line were treated with the polyamine analogue N(1),N(11)-diethylnorspermine or with the polyamine biosynthesis inhibitor 4-amidinoindan-1-one 2'-amidinohydrazone (CGP 48664). The comet assay showed that polyamine depletion resulted in DNA strand breaks. We also show that these DNA strand breaks occurred in cells where there was no expression of gamma-H2AX, which is a marker of DNA double-strand breaks. Thus, our conclusion is that polyamine depletion causes DNA single-strand breaks, which may be the cause for the observed delay in S phase progression. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
DNA and Cell Biology
volume
27
issue
9
pages
511 - 516
publisher
Mary Ann Liebert, Inc.
external identifiers
  • wos:000259126800007
  • scopus:50849135141
ISSN
1044-5498
DOI
10.1089/dna.2008.0750
language
English
LU publication?
yes
id
d2cf5e69-7f94-402c-a10b-ddd5e2443648 (old id 1168809)
date added to LUP
2009-03-06 13:08:37
date last changed
2017-11-05 03:55:49
@article{d2cf5e69-7f94-402c-a10b-ddd5e2443648,
  abstract     = {It is well known that the positively charged polyamines have a DNA-stabilizing function and that polyamine depletion alters chromatin function. We have previously shown that polyamine depletion causes an S phase prolongation, and others have shown that there is an accumulation of Okazaki-like fragments in polyamine-depleted cells. In the present study we have used the comet assay to investigate polyamine depletion-induced DNA strand breaks. Three breast cancer cell lines and one normal-like breast cell line were treated with the polyamine analogue N(1),N(11)-diethylnorspermine or with the polyamine biosynthesis inhibitor 4-amidinoindan-1-one 2'-amidinohydrazone (CGP 48664). The comet assay showed that polyamine depletion resulted in DNA strand breaks. We also show that these DNA strand breaks occurred in cells where there was no expression of gamma-H2AX, which is a marker of DNA double-strand breaks. Thus, our conclusion is that polyamine depletion causes DNA single-strand breaks, which may be the cause for the observed delay in S phase progression.},
  author       = {Johansson, Veronica and Oredsson, Stina and Alm, Kersti},
  issn         = {1044-5498},
  language     = {eng},
  number       = {9},
  pages        = {511--516},
  publisher    = {Mary Ann Liebert, Inc.},
  series       = {DNA and Cell Biology},
  title        = {Polyamine Depletion with Two Different Polyamine Analogues Causes DNA Damage in Human Breast Cancer Cell Lines.},
  url          = {http://dx.doi.org/10.1089/dna.2008.0750},
  volume       = {27},
  year         = {2008},
}