Low-Dose Radiation Response of Primary Keratinocytes and Fibroblasts from Patients with Cervix Cancer

Abstract

The aim of the present study was to examine, using the micronucleus (MN) assay, the low-dose radiation response of normal skin cells from cancer patients and to determine whether the hyper-radiosensitivity (HRS)-like phenomenon occurs in cells of these patients. Primary skin fibroblasts and keratinocytes derived from 40 patients with cervix cancer were studied. After in vitro gamma irradiation with single doses ranging from 0.05 to 4 Gy, MN induction was assessed. For each patient, the linear-quadratic (LQ) model and the induced repair (IR) model were fitted over the whole data set. In fits of the IR model, an HRS-like response after low doses (seen as the deviation over the LQ curve) was demonstrated for the fibroblasts of two patients and for the keratinocytes of four other patients. The alpha(s)/alpha(r) ratio for the six patients ranged from 2.7 to 15.4, whereas the values of the parameter d(c) ranged from 0.13 to 0.36 Gy. No relationship was observed between chromosomal radiosensitivity of fibroblasts and keratinocytes derived from the same donor in the low-dose (0.1-0.25 Gy) region. In conclusion, the fact that low-dose chromosomal hypersensitivity was observed for cells of only six of the patients studied suggests that it is not a common finding in human normal cells and can represent an individual characteristic.

Relative biological effectiveness of the 60-MeV therapeutic proton beam at the Institute of Nuclear Physics (IFJ PAN) in Kraków, Poland

“…To provide evidence to support the claim that RBE is dependent on radiosensitivity, ideally, proton RBE would be determined for two types of skin cells: fibroblasts and keratinocytes (at least twice as resistant as fibroblasts) (Słonina et al 2007). Keratinocytes are target cells involved in acute epidermal reactions to radiotherapy, whereas fibroblasts are target cells responsible for late effects (fibrosis) in skin and other organs (i.e.…”

“…The current study was approved by the Ethical Committee of the Regional Medical Chamber in Kraków. The procedure for obtaining and preparation of the cells was described previously (Słonina et al 2007, 2008). We used fourth- to sixth-passage fibroblasts.…”

“…Our aim was to evaluate the RBE value for the IFJ PAN 60-MeV proton beam and its dependence on the level of survival (dose level) and position in the SOBP or within the Bragg peak of the pristine beam. Skin fibroblasts were chosen firstly because they represent target cells of late-responding tissue (fibrosis) and thus exhibit a low α / β ratio (Bentzen and Joiner 2009), and secondly, because of their known high individual variation in radiosensitivity (Peacock et al 2000; Słonina et al 2007). …”

ATM-Dependent Hyper-Radiosensitivity in Mammalian Cells Irradiated by Heavy Ions

“…For the low effective activation of ATM and the linked ATM-dependent ''early'' G2 checkpoint, it was predicted that G2-phase cells that survive the exposure to doses less than $0.3 Gy will experience an overall reduced fidelity of repair compared with cells in the other phases of the cell cycle, and therefore, these G2-phase cells will be prone to heritable genetic changes (8). Recently, researchers from Poland reported low-dose HRS/IRR in primary keratinocytes and fibroblasts from patients with cervix cancer for micronucleus induction by X-rays (26). Russian researchers found that the HRS/IRR could be observed by the anaphase method and micronucleus assay in X-ray using Chinese hamster V79 cells and human melanoma cells (27).…”

Radiation induced breast cancer risk in BRCA mutation carriers from low-dose radiological exposures: a systematic review

“…Cumulative data are currently in favor of an individual response to medical exposures . Slonina et al firstly revealed that a low-dose hyper-susceptibility could be an individual characteristic (Slonina et al, 2006(Slonina et al, , 2007. These authors highlighted more X-ray radiation-induced DNA damages in human cells (fibroblasts and keratinocytes) from some patients at low-dose.…”