Influence of DNA double‐strand break rejoining on clonogenic survival and micronucleus yield in human cell lines

Akudugu, John; Theron, Therina; Serafin, Antonio; Böhm, Lothar

doi:10.1080/09553002310001655449

Cited by 17 publications

(13 citation statements)

References 33 publications

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“…The level of micronuclei was consistently higher in the MF-exposed cells at all five menadione concentrations used. The micronucleus findings indicate that the enhanced rate of DNA damage removal in the MF-exposed cells did not lead to improved fidelity of DNA repair, consistent with previous findings showing that the rate and fidelity of DNA repair are not necessarily correlated [24], [25]. The findings of the present study actually show an inverse relationship between repair rate and repair fidelity.…”

Section: Discussionsupporting

confidence: 88%

“…This observation (fast repair and increased micronuclei in the MF + menadione exposed cells) might reflect a causal relationship, if one assumes that it reflects dominance of the faster, but more error-prone, non-homologous end joining (NHEJ) repair pathway over the slower, but more precise, homologous recombination (HR) repair pathway [26]. There is evidence that the fast component of DSB rejoining and micronucleus yield are positively correlated [25].…”

Section: Discussionmentioning

confidence: 99%

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Pre-Exposure to 50 Hz Magnetic Fields Modifies Menadione-Induced Genotoxic Effects in Human SH-SY5Y Neuroblastoma Cells

et al. 2011

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BackgroundExtremely low frequency (ELF) magnetic fields (MF) are generated by power lines and various electric appliances. They have been classified as possibly carcinogenic by the International Agency for Research on Cancer, but a mechanistic explanation for carcinogenic effects is lacking. A previous study in our laboratory showed that pre-exposure to ELF MF altered cancer-relevant cellular responses (cell cycle arrest, apoptosis) to menadione-induced DNA damage, but it did not include endpoints measuring actual genetic damage. In the present study, we examined whether pre-exposure to ELF MF affects chemically induced DNA damage level, DNA repair rate, or micronucleus frequency in human SH-SY5Y neuroblastoma cells.Methodology/Principal FindingsExposure to 50 Hz MF was conducted at 100 µT for 24 hours, followed by chemical exposure for 3 hours. The chemicals used for inducing DNA damage and subsequent micronucleus formation were menadione and methyl methanesulphonate (MMS). Pre-treatment with MF enhanced menadione-induced DNA damage, DNA repair rate, and micronucleus formation in human SH-SY5Y neuroblastoma cells. Although the results with MMS indicated similar effects, the differences were not statistically significant. No effects were observed after MF exposure alone.ConclusionsThe results confirm our previous findings showing that pre-exposure to MFs as low as 100 µT alters cellular responses to menadione, and show that increased genotoxicity results from such interaction. The present findings also indicate that complementary data at several chronological points may be critical for understanding the MF effects on DNA damage, repair, and post-repair integrity of the genome.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Pre-Exposure to 50 Hz Magnetic Fields Modifies Menadione-Induced Genotoxic Effects in Human SH-SY5Y Neuroblastoma Cells

et al. 2011

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“…2 where the cell lines with the least G1 depletion showed less MN yield after neutron irradiation, and is consistent with the suggestion that in cell lines lacking a G1-block, there is a progression of DNA damage through S-phase and this incurs a high level of genomic instability (Paulovich et al, 1997). In another study using the glioblastoma cell lines, we demonstrated that while total (20 hours) DNA double-strand-break (DSB) rejoining reflects clonogenic cell survival, fast (2 hours) rejoining influences MN yield (Akudugu et al, 2004). Mammalian cells repair DNA damage mainly by both homologous recombination (HR) and non-homologous end joining (NHEJ) (Sargent et al, 1997;Liang et al, 1998).…”

Section: Discussionsupporting

confidence: 84%

Changes in G1-phase populations in human glioblastoma and neuroblastoma cell lines influence p(66)/Be neutron-induced micronucleus yield

et al. 2004

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“…where, k is a cell type-dependent constant. D0-values were derived from the slope of a linear regression fit according to Equation (1) for SD ≤ 0.1 and absorbed doses not greater than 10 Gy, using cell survival data for 17 cell lines from three different cancer types [36][37][38] , and were subsequently used to calculate transition doses for comparison with those determined from the LQ formalism.…”

Section: Estimation Of D0 From the Multi-target Modelmentioning

confidence: 99%

“…In the following, data for 17 cancer cell lines spanning a wide range of radiosensitivities [36][37][38] , were used to test whether D0, as originally defined, is indeed independent of the level of cell kill. The implications of a potential dependence of D0 on the extent of cell kill on the strength of the LQ model as a predictor of radiosensitivity at high radiation absorbed doses are further discussed.…”

Section: Introductionmentioning

confidence: 99%

Estimation of transition doses for human glioblastoma, neuroblastoma and prostate cell lines using the linear-quadratic formalism

Akudugu

Serafin

2015

Int J Cancer Ther Oncol

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Cite this article as: Akudugu J, Serafin A. Estimation of transition doses for human glioblastoma, neuroblastoma and prostate cell lines using the linear-quadratic formalism. Int J Cancer Ther Oncol 2015; 3(3):3311. Original ArticleAbstract Purpose: The introduction of stereotactic radiotherapy has raised concerns regarding the use of the linear-quadratic (LQ) model for predicting radiation response for large fractional doses. To partly address this issue, a transition dose D* below which the LQ model retains its predictive strength has been proposed. Estimates of D* which depends on the , β, and D0 parameters are much lower than fractional doses typically encountered in stereotactic radiotherapy. D0, often referred to as the final slope of the cell survival curve, is thought to be constant. In vitro cell survival curves generally extend over the first few logs of cell killing, where D0-values derived from the multi-target formalism may be overestimated and can lead to low transition doses. Methods: D0-values were calculated from first principles for each decade of cell killing, using experimentally-determined  and β parameters for 17 human glioblastoma, neuroblastoma, and prostate cell lines, and corresponding transition doses were derived. Results:D0 was found to decrease exponentially with cell killing. Using D0-values at cell surviving fractions of the order of 10 -10 yielded transition doses~3-fold higher than those obtained from D0-values obtained from conventional approaches. D* was found to increase from 7.84 ± 0.56, 8.91 ± 1.20, and 6.55 ± 0.91 Gy to 26.84 ± 2.83, 23.95 ± 2.03, and 22.49 ± 2.31 Gy for the glioblastoma, neuroblastoma, and prostate cell lines, respectively. Conclusion: These findings suggest that the linear-quadratic formalism might be valid for estimating the effect of stereotactic radiotherapy with fractional doses in excess of 20 Gy.D0-values derived from the multi-target formalism. FIG. 5: Plot of D0, derived from LQ parameters, against the decade of cell killing in which D0 is derived for human glioblastoma, neuroblastoma, and prostate cell lines. Symbols representing pooled data from Figures 2-4 are superimposed on fitted curves from historical data for glioblastoma (dotted line) 41 , neuroblastoma (dashed line) 31, 43 and prostate (solid line) 44 cell lines. Large symbols represent D0-values derived from the multi-target formalism from cell survival data for each group of cell lines. 36-38 Error bars represent the standard error of the mean for each set of pooled data.Similarly, D0 declined from 1.85 ± 0.38 to 0.68 ± 0.04 Gy in the neuroblastoma cell lines (Figure 3). For the prostate cell lines, D0 decreased from 2.28 ± 0.23 Gy at high levels of cell survival to 0.81 ± 0.08 Gy at high levels of cell killing (Figure 4). In all cases, D0-values derived from the multi-target formalism were significantly higher than those obtained from the LQ model at a cell survival level of 10 -10 (P  0.0023).The resulting transition doses obtained from D0-values derived from the LQ model were f...

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Influence of DNA double‐strand break rejoining on clonogenic survival and micronucleus yield in human cell lines

Cited by 17 publications

References 33 publications

Pre-Exposure to 50 Hz Magnetic Fields Modifies Menadione-Induced Genotoxic Effects in Human SH-SY5Y Neuroblastoma Cells

Pre-Exposure to 50 Hz Magnetic Fields Modifies Menadione-Induced Genotoxic Effects in Human SH-SY5Y Neuroblastoma Cells

Changes in G1-phase populations in human glioblastoma and neuroblastoma cell lines influence p(66)/Be neutron-induced micronucleus yield

Estimation of transition doses for human glioblastoma, neuroblastoma and prostate cell lines using the linear-quadratic formalism

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