Determination of somatic mutant frequencies at glycophorin A and T-cell receptor loci for biodosimetry of prolonged irradiation

Abstract

The GPA assay has limited potential to be used as a biodosimeter of prolonged irradiation, at least in dose interval up to 2.0 Gy. The TCR assay is likely to have greater potential in estimation of recent radiation exposure than the GPA assay.

Measurement of Mutant Frequency in T-Cell Receptor (Tcr) Gene by Flow Cytometry After X-Irradiation on El-4 Mice Lymphoma Cells

“…The in vivo TCR mutant assays using T-lymphocytes from human (Kyoizumi et al, 1990;Sawada et al, 1998aSawada et al, , 1998b) and mice Umeki et al, 1997) have been established, and the assays have successfully been used to detect radiationinduced mutations in the patients receiving radiotherapy (Iwamoto et al, 1994;Ishioka et al, 1997) and in the population exposed to radiation during the 1986 Chernobyl accident (Saenko et al, 1998(Saenko et al, , 2000. For the in vitro TCR mutant assay, using cultured human Tlymphocytes, we previously reported that X-raysinduced TCR MF at D 37 (giving 37% survival) was 31.7 × 10 −4 and the relationship appears linear between the mutation induction and the doses .…”

“…Although there was no significant doserelated effect observed in atomic bomb survivors, cancer patients who had received radiotherapy (Kyoizumi et al, 1992;Iwamoto et al, 1994;Ishioka et al, 1997) or chemotherapy (Hirota et al, 1994;Sawada et al, 1998a) showed a dose-related increase of TCR mutant frequency (MF). Thus, this assay has been applied to human lymphocytes from people who were directly or indirectly exposed to radiation during and after the Chernobyl accident in Ukraine (Akleyev et al, 1995;Saenko et al, 1998Saenko et al, , 2000Zamulaeva et al, 2006).…”

T-Cell Receptor Mutation Assay for Monitoring Human Genotoxic Exposure

“…It has, for example, been applied to lymphocytes from cancer patients who had recently received radiotherapy [ 17 , 19 , 20 ], from patients who had been treated during the 1930s and 1940s with Thorotrast-a colloidal preparation of radioactive thorium-232 used as a radiological contrast medium [ 19 , 21 ], from a person who was heavily exposed to radiation during the 1986 Chernobyl accident [ 19 ], from cleanup workers in the Chernobyl accident [ 22 ], from residents in a contaminated area near Chelyabinsk in Russia [ 23 , 24 ] and Semipalatinsk in Kazakhstan [ 25 ], and from nuclear workers [ 26 ]. The assay has also been used to monitor genotoxic chemicalexposed donors, including cancer patients who had received chemotherapy [ 27 -29 ] and workers occupationally exposed to cancer drugs [ 29 -31 ] and lead [ 32 -35 ].…”

Analysis of Erythrocyte Glycophorin‐A Variants by Flow Cytometry in Lung Disease Patients Detects the Effect of Tobacco Smoke

“…The GPA assay was proposed to provide an evaluation of the life-span cumulative exposure for humans, because it detects mutations preserved at the level of red blood stem cells during the lifetime of an individual. GPA variants were found to be at significantly increased frequency among Hiroshima A-bomb survivors; the assay was tentatively used as a biodosimeter of cumulative exposure after the fall-out in the Chernobyl nuclear power center [2,5,9,16,18,26]. The GPA assay by FCM was also used for monitoring the genotoxic load in cancer patients who underwent radio-or chemotherapy [4,12,15,22,24,27], in workers exposed to styrene [6,10] and, in association with DNA adducts, for foundry workers exposed to polycyclic aromatic hydrocarbons [25].…”