An association between the radiation-induced arrest of G2-phase cells and low-dose hyper-radiosensitivity: A plausible underlying mechanism?

Brian Marples, B. G. Wouters, M. C. Joiner

Research output: Contribution to journalArticle

92 Citations (Scopus)

Abstract

The survival of asynchronous and highly enriched G1-, S- and G2-phase populations of Chinese hamster V79 cells was measured after irradiation with 60Co γ rays (0.1-10 Gy) using a precise flow cytometry-based clonogenic survival assay. The high-dose survival responses demonstrated a conventional relationship, with G2-phase cells being the most radiosensitive and S-phase cells the most radioresistant. Below 1 Gy, distinct low-dose hyper-radiosensitivity (HRS) responses were observed for the asynchronous and G2-phase enriched cell populations, with no evidence of HRS in the G1- and S-phase populations. Modeling supports the conclusion that HRS in asynchronous V79 populations is explained entirely by the HRS response of G2-phase cells. An association was discovered between the occurrence of HRS and the induction of a novel G2-phase arrest checkpoint that is specific for cells that are in the G2 phase of the cell cycle at the time of irradiation. Human T98G cells and hamster V79 cells, which both exhibit HRS in asynchronous cultures, failed to arrest the entry into mitosis of damaged G2-phase cells at doses less than 30 cGy, as determined by the flow cytometric assessment of the phosphorylation of histone H3, an established indicator of mitosis. In contrast, human U373 cells that do not show HRS induced this G2-phase checkpoint in a dose-independent manner. These data suggest that HRS may be a consequence of radiation-damaged G2-phase cells prematurely entering mitosis.

Original languageEnglish (US)
Pages (from-to)38-45
Number of pages8
JournalRadiation Research
Volume160
Issue number1
DOIs
StatePublished - Jul 1 2003
Externally publishedYes

Fingerprint

G2 Phase
Radiation Tolerance
radiation tolerance
Radiation
dosage
radiation
cells
mitosis
S Phase
Mitosis
G2 Phase Cell Cycle Checkpoints
hamsters
Population
Survival
phosphorylation
irradiation
cytometry
G1 Phase
entry
Cricetulus

ASJC Scopus subject areas

  • Biophysics
  • Radiation
  • Radiology Nuclear Medicine and imaging

Cite this

An association between the radiation-induced arrest of G2-phase cells and low-dose hyper-radiosensitivity : A plausible underlying mechanism? / Marples, Brian; Wouters, B. G.; Joiner, M. C.

In: Radiation Research, Vol. 160, No. 1, 01.07.2003, p. 38-45.

Research output: Contribution to journalArticle

@article{9a3e45a057b647648735b3af8266e2a1,
title = "An association between the radiation-induced arrest of G2-phase cells and low-dose hyper-radiosensitivity: A plausible underlying mechanism?",
abstract = "The survival of asynchronous and highly enriched G1-, S- and G2-phase populations of Chinese hamster V79 cells was measured after irradiation with 60Co γ rays (0.1-10 Gy) using a precise flow cytometry-based clonogenic survival assay. The high-dose survival responses demonstrated a conventional relationship, with G2-phase cells being the most radiosensitive and S-phase cells the most radioresistant. Below 1 Gy, distinct low-dose hyper-radiosensitivity (HRS) responses were observed for the asynchronous and G2-phase enriched cell populations, with no evidence of HRS in the G1- and S-phase populations. Modeling supports the conclusion that HRS in asynchronous V79 populations is explained entirely by the HRS response of G2-phase cells. An association was discovered between the occurrence of HRS and the induction of a novel G2-phase arrest checkpoint that is specific for cells that are in the G2 phase of the cell cycle at the time of irradiation. Human T98G cells and hamster V79 cells, which both exhibit HRS in asynchronous cultures, failed to arrest the entry into mitosis of damaged G2-phase cells at doses less than 30 cGy, as determined by the flow cytometric assessment of the phosphorylation of histone H3, an established indicator of mitosis. In contrast, human U373 cells that do not show HRS induced this G2-phase checkpoint in a dose-independent manner. These data suggest that HRS may be a consequence of radiation-damaged G2-phase cells prematurely entering mitosis.",
author = "Brian Marples and Wouters, {B. G.} and Joiner, {M. C.}",
year = "2003",
month = "7",
day = "1",
doi = "10.1667/RR3013",
language = "English (US)",
volume = "160",
pages = "38--45",
journal = "Radiation Research",
issn = "0033-7587",
publisher = "Radiation Research Society",
number = "1",

}

TY - JOUR

T1 - An association between the radiation-induced arrest of G2-phase cells and low-dose hyper-radiosensitivity

T2 - A plausible underlying mechanism?

AU - Marples, Brian

AU - Wouters, B. G.

AU - Joiner, M. C.

PY - 2003/7/1

Y1 - 2003/7/1

N2 - The survival of asynchronous and highly enriched G1-, S- and G2-phase populations of Chinese hamster V79 cells was measured after irradiation with 60Co γ rays (0.1-10 Gy) using a precise flow cytometry-based clonogenic survival assay. The high-dose survival responses demonstrated a conventional relationship, with G2-phase cells being the most radiosensitive and S-phase cells the most radioresistant. Below 1 Gy, distinct low-dose hyper-radiosensitivity (HRS) responses were observed for the asynchronous and G2-phase enriched cell populations, with no evidence of HRS in the G1- and S-phase populations. Modeling supports the conclusion that HRS in asynchronous V79 populations is explained entirely by the HRS response of G2-phase cells. An association was discovered between the occurrence of HRS and the induction of a novel G2-phase arrest checkpoint that is specific for cells that are in the G2 phase of the cell cycle at the time of irradiation. Human T98G cells and hamster V79 cells, which both exhibit HRS in asynchronous cultures, failed to arrest the entry into mitosis of damaged G2-phase cells at doses less than 30 cGy, as determined by the flow cytometric assessment of the phosphorylation of histone H3, an established indicator of mitosis. In contrast, human U373 cells that do not show HRS induced this G2-phase checkpoint in a dose-independent manner. These data suggest that HRS may be a consequence of radiation-damaged G2-phase cells prematurely entering mitosis.

AB - The survival of asynchronous and highly enriched G1-, S- and G2-phase populations of Chinese hamster V79 cells was measured after irradiation with 60Co γ rays (0.1-10 Gy) using a precise flow cytometry-based clonogenic survival assay. The high-dose survival responses demonstrated a conventional relationship, with G2-phase cells being the most radiosensitive and S-phase cells the most radioresistant. Below 1 Gy, distinct low-dose hyper-radiosensitivity (HRS) responses were observed for the asynchronous and G2-phase enriched cell populations, with no evidence of HRS in the G1- and S-phase populations. Modeling supports the conclusion that HRS in asynchronous V79 populations is explained entirely by the HRS response of G2-phase cells. An association was discovered between the occurrence of HRS and the induction of a novel G2-phase arrest checkpoint that is specific for cells that are in the G2 phase of the cell cycle at the time of irradiation. Human T98G cells and hamster V79 cells, which both exhibit HRS in asynchronous cultures, failed to arrest the entry into mitosis of damaged G2-phase cells at doses less than 30 cGy, as determined by the flow cytometric assessment of the phosphorylation of histone H3, an established indicator of mitosis. In contrast, human U373 cells that do not show HRS induced this G2-phase checkpoint in a dose-independent manner. These data suggest that HRS may be a consequence of radiation-damaged G2-phase cells prematurely entering mitosis.

UR - http://www.scopus.com/inward/record.url?scp=0037668069&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037668069&partnerID=8YFLogxK

U2 - 10.1667/RR3013

DO - 10.1667/RR3013

M3 - Article

C2 - 12816521

AN - SCOPUS:0037668069

VL - 160

SP - 38

EP - 45

JO - Radiation Research

JF - Radiation Research

SN - 0033-7587

IS - 1

ER -