Mutations and chromosomal aberrations in hMTH1-transfected and non-transfected TK6 cells after exposure to low dose rates of gamma radiation

Abstract

The aim of the present study was to analyse the dose rate effect of gamma radiation at the level of mutations, chromosomal aberrations, and cell growth in TK6 cells with normal as well as reduced levels of hMTH1 protein. TK6 cells were exposed to gamma radiation at dose rates ranging from 1.4 to 30.0 mGy/h (chronic exposure) as well as 24 Gy/h (acute exposure). Cell growth, frequency of thymidine kinase mutants, and of chromosomal aberrations in painted chromosomes 2, 8, and 14 were analysed. A decline in cell growth and an increase in unstable-type chromosomal aberrations with increasing dose rate were observed in both cell lines. A dose rate effect was not seen on mutations or stable-type chromosomal aberrations in any of the two cell lines. Reduction in the hMTH1 protein does not influence the sensitivity of TK6 cells to gamma radiation. This result fits well with data of others generated with the same cell line.

Biological effectiveness of very high gamma dose rate and its implication for radiological protection

“…Numerous results have demonstrated that reducing the dose rate below the HDR range exerts a sparing effect on cell killing due to improved repair of sub-lethal damage (Badie et al 1996 ; Bedford et al 1978 ). For the same reason, the frequency of unstable chromosomal aberrations and micronuclei is reduced per unit dose when the dose rate is reduced below HDR (Bauchinger et al 1979 ; Manesh et al 2014 ; Tanaka et al 2009 ; Vral et al 1992 ).…”

“…Later, animal studies on cancer and non-cancer stochastic effects confirmed the existence of DDREF (reviewed in Little 2018 ). Results of cell experiments which focused on mutations and stable-type chromosomal aberrations that can be regarded as molecular events related to cancer (Beroukhim et al 2007 ) are contradictory, with some showing no or little sparing effect of LDR (Evans et al 1990 ; Manesh et al 2014 ) and other demonstrating clear effects (Kiefer et al 2002 ) (reviewed in Manesh et al 2014 ).…”

“…In all the above studies that were triggered by the desire to validate the LSS-derived risk factors in a chronic exposure scenario, the biological effectiveness of LDR radiation was compared to HDR radiation that was not higher than ca 1.0 Gy/min. Exemplary HDR values were 0.3 Gy/min (Grosovsky and Little 1985 ), 0.3 Gy/min (Ueno et al 1982 ), 0.4 Gy/min (Manesh et al 2014 ), 0.5 Gy/min (Furuno-Fukushi et al 1988 ), 0.5 Gy/min (Lorenz et al 1994 ), 0.5 Gy/min (Nakamura and Okada 1981 ), 0.70–0.79 Gy/min (Russell et al 1958 ), and 0.83 Gy/min (Evans et al 1990 ). These values are much lower than the tens of Gy/min following the atomic bomb detonations in Hiroshima and Nagasaki (Ruhm et al 2018 ).…”

“…The validity of a DDREF has been questioned (Jacob et al 2009 ) and the ICRP is investigating whether, in the light of new scientific results, its use is still justified (Ruhm et al 2015 , 2016 ). The criticism of DDREF is in part based on results of cell experiments which show that, per unit dose, the level of radiation-induced DNA mutations and stable-type chromosomal aberrations is the same after exposure to radiation at a high and low dose rate (Manesh et al 2014 and the papers within).…”

Typical doses and dose rates in studies pertinent to radiation risk inference at low doses and low dose rates

“…Endpoints such as chromosomal aberrations and mutations have been assessed at dose rates as low as 20 mGy/d with accumulated doses of 8 Gy [ 13 ]; more commonly dose rates of 1–10 mGy/h are reported with accumulated doses of 0.5 to several Gray (e.g. Okudaira et al [ 14 ]; Manesh et al [ 15 ]). Reference [ 16 ], a review specifically considering cellular and molecular data suitable for dose rate effect evaluation, provides a more extensive summary and tabulation of the irradiation conditions used in the relevant studies.…”