The effect of oxygen concentration on the X-ray induction of chromosome aberrations in human lymphocytes

Prosser, J.; White, C. M.; Edwards, Alan

doi:10.1016/0027-5107(79)90134-9

Cited by 11 publications

(3 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Many other groups have proposed using the OER concept to incorporate the effects of hypoxia into modeling of in vitro and in vivo radiation responses. Although the concept of an OER has been applied to end points such as DSB induction 29,53,61 and chromosomal aberrations, 62,63 the OER is usually defined as the dose under conditions of extreme hypoxia divided by the dose under conditions of partial oxygen pressure to achieve the same level of cell killing. A disadvantage of defining OER in terms of cell killing ͑or survival͒ is that the OER becomes a function of dose 44,47 and dose rate.…”

Section: Discussionmentioning

confidence: 99%

Effects of oxygen on intrinsic radiation sensitivity: A test of the relationship between aerobic and hypoxic linear-quadratic (LQ) model parametersa)

2006

View full text Add to dashboard Cite

The poor treatment prognosis for tumors with high levels of hypoxia is usually attributed to the decreased sensitivity of hypoxic cells to ionizing radiation. Mechanistic considerations suggest that linear quadratic (LQ) survival model radiosensitivity parameters for hypoxic (H) and aerobic (A) cells are related by alphaH = alphaA/oxygen enhancement ratio (OER) and (alpha/beta)H=OER(alpha/beta)A. The OER parameter may be interpreted as the ratio of the dose to the hypoxic cells to the dose to the aerobic cells required to produce the same number of DSBs per cell. The validity of these expressions is tested against survival data for mammalian cells irradiated in vitro with low- and high-LET radiation. Estimates of hypoxic and aerobic radiosensitivity parameters are derived from independent and simultaneous least-squares fits to the survival data. An external bootstrap procedure is used to test whether independent fits to the survival data give significantly better predictions than simultaneous fits to the aerobic and hypoxic data. For low-LET radiation, estimates of the OER derived from the in vitro data are between 2.3 and 3.3 for extreme levels of hypoxia. The estimated range for the OER is similar to the oxygen enhancement ratios reported in the literature for the initial yield of DSBs. The half-time for sublethal damage repair was found to be independent of oxygen concentration. Analysis of patient survival data for cervix cancer suggests an average OER less than or equal to 1.5, which corresponds to a pO2 of 5 mm Hg (0.66%) in the in vitro experiments. Because the OER derived from the cervix cancer data is averaged over cells at all oxygen levels, cells irradiated in vivo under extreme levels of hypoxia (<0.5 mm Hg) may have an OER substantially higher than 1.5. The reported analyses of in vitro data, as well as mechanistic considerations, provide strong support for the expressions relating hypoxic and aerobic radiosensitivity parameters. The formulas are also useful for the analysis of clinical data because the number of radiosensitivity parameters that need to be determined is reduced from four to three without a substantial decrease in the ability of the LQ to accurately predict the surviving faction. The relationships among radiosensitivity parameters imply that the dose to the hypoxic subvolume of the tumor needs to be escalated by a factor of the OER to achieve the same level of tumor control as in well oxygenated tumor regions.

show abstract

Section: Discussionmentioning

confidence: 99%

Effects of oxygen on intrinsic radiation sensitivity: A test of the relationship between aerobic and hypoxic linear-quadratic (LQ) model parametersa)

2006

View full text Add to dashboard Cite

show abstract

“…If true, the decreased (average) complexity of the clusters formed under reduced oxygen conditions may enhance the accuracy of cluster repair. For end points such as chromosomal aberrations (41,42) and cell death (32,33,36,39,(43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53)(54)(55)(56)(57), the decreased sensitivity of hypoxic cells to ionizing radiation may be due in part to an increase in the accuracy of repair as well as to a reduction in the initial number of clusters a cell must repair.…”

Section: Introductionmentioning

confidence: 99%

Effects of Radiation Quality and Oxygen on Clustered DNA Lesions and Cell Death

et al. 2011

View full text Add to dashboard Cite

Radiation quality and cellular oxygen concentration have a substantial impact on DNA damage, reproductive cell death and, ultimately, the potential efficacy of radiation therapy for the treatment of cancer. To better understand and quantify the effects of radiation quality and oxygen on the induction of clustered DNA lesions, we have now extended the Monte Carlo Damage Simulation (MCDS) to account for reductions in the initial lesion yield arising from enhanced chemical repair of DNA radicals under hypoxic conditions. The kinetic energy range and types of particles considered in the MCDS have also been expanded to include charged particles up to and including (56)Fe ions. The induction of individual and clustered DNA lesions for arbitrary mixtures of different types of radiation can now be directly simulated. For low-linear energy transfer (LET) radiations, cells irradiated under normoxic conditions sustain about 2.9 times as many double-strand breaks (DSBs) as cells irradiated under anoxic conditions. New experiments performed by us demonstrate similar trends in the yields of non-DSB (Fpg and Endo III) clusters in HeLa cells irradiated by γ rays under aerobic and hypoxic conditions. The good agreement among measured and predicted DSBs, Fpg and Endo III cluster yields suggests that, for the first time, it may be possible to determine nucleotide-level maps of the multitude of different types of clustered DNA lesions formed in cells under reduced oxygen conditions. As particle LET increases, the MCDS predicts that the ratio of DSBs formed under normoxic to hypoxic conditions by the same type of radiation decreases monotonically toward unity. However, the relative biological effectiveness (RBE) of higher-LET radiations compared to (60)Co γ rays (0.24 keV/μm) tends to increase with decreasing oxygen concentration. The predicted RBE of a 1 MeV proton (26.9 keV/μm) relative to (60)Co γ rays for DSB induction increases from 1.9 to 2.3 as oxygen concentration decreases from 100% to 0%. For a 12 MeV (12)C ion (681 keV/μm), the 'predicted RBE for DSB induction increases from 3.4 (100% O(2)) to 9.8 (0% O(2)). Estimates of linear-quadratic (LQ) cell survival model parameters (α and β) are closely correlated to the Monte Carlo-predicted trends in DSB induction for a wide range of particle types, energies and oxygen concentrations. The analysis suggests α is, as a first approximation, proportional to the initial number of DSBs per cell, and β is proportional to the square of the initial number of DSBs per cell. Although the reported studies provide some evidence supporting the hypothesis that DSBs are a biologically critical form of clustered DNA lesion, the induction of Fpg and Endo III clusters in HeLa cells irradiated by γ rays exhibits similar trends with oxygen concentration. Other types of non-DSB cluster may still play an important role in reproductive cell death. The MCDS captures many of the essential trends in the formation of clustered DNA lesions by ionizing radiation and provides useful information to probe the mu...

show abstract

“…[6]. The open symbols represent data from the following publications: (O) neutrons [3,12], (•) a-particles (a = 0.27 Gy -1 for 242Cm, a = 0.37 Gy -1 for 239pu) [10], (ZX) 150 kV, 30 kV, and 10 kV X-rays and 13 MeV-electrons [20,21], (V) 6°Co y-rays and 250 kV X-rays [tl, 12], (~) 250 kV X-rays [13], (@) 6°Co F-rays [19], and (@) 3 MeV electrons [15]. The dashed curve represents an eye-fit which serves to indicate the general trend of the data In Figure 2 the linear-term coefficients a are plotted as a function of the track average LET, chosen here as the parameter characterizing radiation quality.…”

Section: Discussionmentioning

confidence: 99%

Numerical relationship between cells with radiation-induced chromosome aberrations and cells lethally injured by radiation

Harder

1980

Radiat Environ Biophys

View full text Add to dashboard Cite

The numerical relationship between radiation-induced chromosome aberrations in human G0 lymphocytes and reproductive lethality of human bone-marrow lymphocytes is analysed within a large LET interval. The comparison is based upon the evaluation of the coefficient a of the linear component of the corresponding dose-effect-relation for the frequency of cells without aberrations and for the frequency of surviving cells respectively. The good correlation between these coefficients over a large LET interval supports the hypothesis that structural chromosome aberrations and reproductive cell death both result from the same gross chromatin damage.

show abstract

The effect of oxygen concentration on the X-ray induction of chromosome aberrations in human lymphocytes

Cited by 11 publications

References 17 publications

Effects of oxygen on intrinsic radiation sensitivity: A test of the relationship between aerobic and hypoxic linear-quadratic (LQ) model parametersa)

Effects of oxygen on intrinsic radiation sensitivity: A test of the relationship between aerobic and hypoxic linear-quadratic (LQ) model parametersa)

Effects of Radiation Quality and Oxygen on Clustered DNA Lesions and Cell Death

Numerical relationship between cells with radiation-induced chromosome aberrations and cells lethally injured by radiation

Contact Info

Product

Resources

About