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

S. M. Cohn; B. R. Krawisz; S. L. Dresler; M. W. Lieberman

doi:10.1073/pnas.81.15.4828

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

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

Research output: Contribution to journal › Article › peer-review

25 Scopus citations

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 language	English (US)
Pages (from-to)	4828-4832
Number of pages	5
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	81
Issue number	15 I
DOIs	https://doi.org/10.1073/pnas.81.15.4828
State	Published - 1984
Externally published	Yes

ASJC Scopus subject areas

General

Access to Document

10.1073/pnas.81.15.4828

Cite this

@article{28e96a64d8c94f2eaa7d2b1ba9b35370,

title = "Induction of replicative DNA synthesis in quiescent human fibroblasts by DNA damaging agents",

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.",

author = "Cohn, {S. M.} and Krawisz, {B. R.} and Dresler, {S. L.} and Lieberman, {M. W.}",

year = "1984",

doi = "10.1073/pnas.81.15.4828",

language = "English (US)",

volume = "81",

pages = "4828--4832",

journal = "Proceedings of the National Academy of Sciences of the United States of America",

issn = "0027-8424",

publisher = "National Academy of Sciences",

number = "15 I",

}

TY - JOUR

T1 - Induction of replicative DNA synthesis in quiescent human fibroblasts by DNA damaging agents

AU - Cohn, S. M.

AU - Krawisz, B. R.

AU - Dresler, S. L.

AU - Lieberman, M. W.

PY - 1984

Y1 - 1984

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0021263016&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0021263016&partnerID=8YFLogxK

U2 - 10.1073/pnas.81.15.4828

DO - 10.1073/pnas.81.15.4828

M3 - Article

C2 - 6589629

AN - SCOPUS:0021263016

SN - 0027-8424

VL - 81

SP - 4828

EP - 4832

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

IS - 15 I

ER -

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

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this