Low-dose hyper-radiosensitivity of progressive and regressive cells isolated from a rat colon tumour: Impact of DNA repair

Abstract

HRS response of PRO subline may be induced by impairments in NHEJ repair that targets G(1) cells and RAD51-dependent repair that targets S-G(2)/M cells. The cellular consequences of such impairments are a failure to arrest in cell cycle, the propagation of damage through cell cycle, mitotic death but not p53-dependent apoptosis. Tumourigenic cells with high metastatic potential may preferentially show HRS response.

Determining if low dose hyper-radiosensitivity (HRS) can be exploited to provide a therapeutic advantage: A cell line study in four glioblastoma multiforme (GBM) cell lines

“…These data suggest that the therapeutic benefit can be maintained if the sizes of the individual pulses in the ultra-fractionation schedule remain within the HRS/IRR transitional dose range. The concept of enhanced cytotoxicity after ultrafractionation is consistent with the data reported by Collis et al (2004) and Thomas et al (2008) for evading the activation of ATM-dependent repair processes after low dose rate treatments.…”

“…The increased sensitivity of cells to acute doses below ~0.3-0.4 Gy has been defined by the term low-dose hyper-radiosensitivity (HRS) (Marples and Joiner 1993) and has been linked with absent, ineffectual or defective DNA (Deoxyribonucleic acid) repair processes (Skov 1999, Vaganay-Juery et al 2000, Marples et al 2002, Wykes et al 2006, Thomas et al 2008. As the dose increases above 0.4 Gy, increasing levels of DNA damage lead to the activation of repair processes that manifest as increased radioresistance (IRR).…”

Specific molecular and cellular events induced by irradiated X-ray photoactivatable drugs raise the problem of co-toxicities: particular consequences for anti-cancer synchrotron therapy

“…3c). Altogether, these data suggest that the yield of HDCs increases with the severity of DSBs and might be the result of an uncontrolled nuclease activity in response to unrepairable DSBs, as has been suggested earlier (Thomas et al, 2008), that may lead to a severe chromatin decondensation. Hence, the yield of HDCs may serve also as a sensor of toxicity for radiochemotherapy involving photoactivatable drugs.…”

Low dose hypersensitivity following in vitro cell irradiation with charged particles: Is the mechanism the same as with X-ray radiation?

“…A great amount of data about HRS after irradiation with sparsely ionizing radiation, like X-or g-rays is available in the literature (Vaganay-Juery et al 2000, Rothkamm and Löbrich 2003, Wykes et al 2006, Thomas et al 2008. Usually, clonogenic assays following in vitro cell irradiation result in a linear quadratic behavior of the survival fraction (SF):…”