Induction of replicative DNA synthesis in quiescent human fibroblasts by DNA damaging agents

Steven Cohn, B. R. Krawisz, S. L. Dresler, M. W. Lieberman

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

A marked induction of DNA replication was observed in confluent human diploid fibroblast cultures treated with low relatively nontoxic doses of UV radiation, N-methyl-N-nitrosourea (MNU), and N-acetoxy-2-acetylaminofluorene (AAAF). Isopycnic CsCl density gradient analysis of newly synthesized DNA labeled with BrdUrd indicated that most of the synthesis was semiconservative. The rate of semiconservative DNA synthesis was maximal 24 hr after damage. This induction of DNA replication was greatest at ~3 J/m2 UV, 0.5 mM MNU, or 1.0 μM AAAF; was inhibited by hydroxyurea and aphidicolin; and also occurred in repair-deficient xeroderma pigmentosum fibroblasts. Autoradiographic examination of both confluent cultures and serum-arrested cultures showed a large increase in the fraction of densely labeled (S phase) cells after UV treatment. These densely labeled cells retain the capacity for cell division and subsequent proliferation. We conclude that low doses of at least three different DNA damaging agents are capable of recruiting quiescent cells into a state of DNA replication similar to that observed in the normal cell cycle.

Original languageEnglish (US)
Pages (from-to)4828-4832
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume81
Issue number15 I
StatePublished - Jan 1 1984
Externally publishedYes

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DNA Replication
Methylnitrosourea
Fibroblasts
DNA
Acetoxyacetylaminofluorene
Aphidicolin
2-Acetylaminofluorene
Xeroderma Pigmentosum
Hydroxyurea
Diploidy
S Phase
Cell Division
Cell Cycle
Radiation
Serum

ASJC Scopus subject areas

  • General
  • Genetics

Cite this

Induction of replicative DNA synthesis in quiescent human fibroblasts by DNA damaging agents. / Cohn, Steven; Krawisz, B. R.; Dresler, S. L.; Lieberman, M. W.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 81, No. 15 I, 01.01.1984, p. 4828-4832.

Research output: Contribution to journalArticle

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