Clinically relevant radioresistant cells efficiently repair DNA double‐strand breaks induced by X‐rays

Kuwahara, Yoshikazu; Li, Li; Baba, Taisuke; Nakagawa, Hiroe; Shimura, Tsutomu; Yamamoto, Yoichiro; Ohkubo, Yasuhito; Fukumoto, Manabu

doi:10.1111/j.1349-7006.2009.01082.x

Cited by 55 publications

(71 citation statements)

References 41 publications

(47 reference statements)

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“…The possible activation of the HR pathway to repair dsbs in CRR cells was eliminated by immunostaining for RAD51 foci. Our previous data showed that the number of cells in the G2 phase of the cell cycle is more abundant in CRR cells than in parental cells [1]. High-fidelity NHEJ in G2 might be involved in DNA repair in CRR cells.…”

Section: Resultsmentioning

confidence: 93%

“…Several reports suggest that radioresistance is associated with the enhanced repair of radiation-induced DNA damage [1] [7] [18] [19]. Our previous study also showed that X-ray-induced phosphorylated histone H2AX (γH2AX) foci disappear more rapidly in HepG2-8960-R than in parental HepG2 [1].…”

Section: Introductionmentioning

confidence: 83%

“…The molecular basis of radioresistance remains to be elucidated. The radioresistant phenotype has been correlated with characteristics such as the enhanced repair of IR-induced DNA damage [1] [2] [3] [4], overexpression of cyclin D1 [5] [6], higher rates of cell growth and migration [7], a lower concentration of reactive oxygen species (ROS) in cells [8] [9] [10], inactivation of apoptotic proteins [11] and alterations in radiation-induced autophagy [12] [13]. A disadvantage of studying radioresistance is the lack of adequate radioresistant models reflecting the clinical features of this phenomenon.…”

Section: Introductionmentioning

confidence: 99%

“…The inherent variation among cells with different origins makes it difficult to determine the extent to which candidate factors contribute to cellular radioresistance and to identify factors that are essential for radioresistance. Isogenic models consisting of cells from the same origin that differ only in radioresistance have been increasingly pivotal in elucidating the cellular mechanisms of radioresistance [1] [7] [10] [14]. These models avoid the influence of confounding factors, allowing one to unravel the molecular mechanisms that are truly involved in radioresistance.…”

Section: Introductionmentioning

confidence: 99%

“…To elucidate the molecular mechanisms underlying cellular radioresistance, we established clinically relevant radioresistant (CRR) cell lines from several hu-Y. Kuwahara et al man cancer cell lines via long-term exposure to X-rays with stepwise dose escalation [1]. By definition, CRR cells continue to proliferate despite exposure to 2 Gy X-rays/day for more than 30 days.…”

Section: Introductionmentioning

confidence: 99%

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X-Ray Induced Mutation Frequency at the <i>Hypoxanthine Phosphoribosyltransferase</i> Locus in Clinically Relevant Radioresistant Cells

Kuwahara¹,

Roudkenar²,

Urushihara³

et al. 2017

IJMPCERO

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To elucidate the molecular mechanisms underlying cellular radioresistance, clinically relevant radioresistant cell lines were established via long-term exposure to X-rays with stepwise dose escalation. Established cells continue to proliferate despite exposure to 2 Gy X-rays/day for more than 30 days, a standard protocol in cancer radiotherapy. DNA repair fidelity in radioresistant and the parental cells by evaluating the mutation frequency at the hypoxanthine phosphoribosyltransferase (HPRT) locus after exposure to X-rays was determined. Mutation spectrum at the HPRT locus was examined by multiplex polymerase chain reaction. Rejoining kinetics of X-ray-induced DNA double strand breaks (dsbs) was evaluated by the detection of phosphorylated histone H2AX (γH2AX) after X-irradiation. The fold increase in the HPRT mutation frequency due to acute radiation was similar between radioresistant and the parental cell lines. However, fractionated radiation (FR) consisting of 2 Gy X-rays/day increased the mutation frequency at the HPRT locus in parental but not in radioresistant cells. Analysis of the FR-induced mutations at the HPRT locus revealed a high frequency of deletion mutations (>70%) in parental but not in

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Section: Resultsmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 83%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

X-Ray Induced Mutation Frequency at the <i>Hypoxanthine Phosphoribosyltransferase</i> Locus in Clinically Relevant Radioresistant Cells

Kuwahara¹,

Roudkenar²,

Urushihara³

et al. 2017

IJMPCERO

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Loss of EGF‐dependent cell proliferation ability on radioresistant cell HepG2‐8960‐R

Saito

Abiko

Kishida

et al. 2015

Cell Biochemistry & Function

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Acquired radioresistance of cancer cells interferes with radiotherapy and increases the probability of cancer recurrence. HepG2-8960-R, which is one of several clinically relevant radioresistant (CRR) cell lines, has a high tolerance to the repeated clinically relevant doses of X-ray radiation. In this study, HepG2-8960-R had slightly lower cell proliferation ability than HepG2 in the presence of FBS. In particular, epidermal growth factor (EGF) hardly enhanced cell proliferation and DNA synthesis in HepG2-8960-R. Additionally, EGF could not induce the activation of Erk1/2, because the expression of EGF receptor (EGFR) protein decreased in HepG2-8960-R in accordance with the methylation of the EGFR promoter region. Therefore, cetuximab did not inhibit HepG2-8960-R cell proliferation. Our study showed that HepG2-8960-R had radioresistant and cetuximab-resistant abilities.

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Micronucleated erythrocytes in peripheral blood from neonate rats fed by nursing mothers exposed to X‐rays

Solórzano-Meléndez

Rodrigo‐Alarcón

Gómez‐Meda

et al. 2021

Environ and Mol Mutagen

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Most women with breast cancer can become pregnant and give birth while undergoing radiation therapy and breastfeeding is generally not contraindicated. The induction of long‐lived reactive species in proteins, such as casein by X‐ray radiation and DNA damage to unexposed organisms, has been shown when ingesting irradiated cheese. To determine whether exposing lactating rats to X‐rays increases the number of micronucleated erythrocytes (MNEs) in peripheral blood of their unexposed or breastfeeding rat pups, 15 female Wistar rats were divided into three groups: Negative control; Experimental group exposed to X‐rays, and group exposed to X‐rays plus vitamin C. The mothers of groups 2 and 3 were irradiated for three consecutive days after giving birth, returning them to their respective cages each time to continue lactation. A blood sample was taken from the mothers and pups at 0, 24, and 48 hr. Blood smears were stained with acridine orange to analyze MNEs. In mother rats, the frequency of micronucleated polychromatic erythrocytes (MNPCEs) increased significantly at 24 and 48 hr in both study groups exposed to radiation. Likewise, in rat pups the MNPCE and MNE frequencies increased in both groups with radiation and radiation plus vitamin C at 24 and 48 hr, and a protection from vitamin C was observed. In conclusion, the genotoxic damage produced in rat pups that were lactated by mothers irradiated with X‐rays is possibly due to the effect of long‐lived reactive species that were formed in the breast milk of female Wistar rats during the irradiation process.

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Clinically relevant radioresistant cells efficiently repair DNA double‐strand breaks induced by X‐rays

Cited by 55 publications

References 41 publications

X-Ray Induced Mutation Frequency at the <i>Hypoxanthine Phosphoribosyltransferase</i> Locus in Clinically Relevant Radioresistant Cells

X-Ray Induced Mutation Frequency at the <i>Hypoxanthine Phosphoribosyltransferase</i> Locus in Clinically Relevant Radioresistant Cells

Loss of EGF‐dependent cell proliferation ability on radioresistant cell HepG2‐8960‐R

Micronucleated erythrocytes in peripheral blood from neonate rats fed by nursing mothers exposed to X‐rays

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Clinically relevant radioresistant cells efficiently repair DNA double‐strand breaks induced by X‐rays

Cited by 55 publications

References 41 publications

X-Ray Induced Mutation Frequency at the &lt;i&gt;Hypoxanthine Phosphoribosyltransferase&lt;/i&gt; Locus in Clinically Relevant Radioresistant Cells

X-Ray Induced Mutation Frequency at the &lt;i&gt;Hypoxanthine Phosphoribosyltransferase&lt;/i&gt; Locus in Clinically Relevant Radioresistant Cells

Loss of EGF‐dependent cell proliferation ability on radioresistant cell HepG2‐8960‐R

Micronucleated erythrocytes in peripheral blood from neonate rats fed by nursing mothers exposed to X‐rays

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Product

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X-Ray Induced Mutation Frequency at the <i>Hypoxanthine Phosphoribosyltransferase</i> Locus in Clinically Relevant Radioresistant Cells

X-Ray Induced Mutation Frequency at the <i>Hypoxanthine Phosphoribosyltransferase</i> Locus in Clinically Relevant Radioresistant Cells