Table 2.

Relevant references related to the effect of dose rate on mutation induction

Type of animal/strain or in vitro cell type	Irradiation details	Outcomes recorded, time post-exposure	Definitive findings	Reference
TK6 and WTK1 human lymphoblasts	γ-irradiation Doses: up to 6 Gy Dose rates: 27, 67, 143 mGy/h and 6 × 104 mGy/h	HPRT mutations, survival, cell growth, cell cycle distribution,	Compared with acute doses, the low dose rates protected against mutation induction at the hrpt locus in WTK1, but protection was inversely related to dose rate. Slight inverse dose-rate effect in TK6, with mutation induction at the lowest dose-rate exceeding that at acute exposures	Amundson and Chen (1996)
human lymphoblastoid WIL2-NS cells	γ-irradiation Doses: up to 5 Gy Dose rates: 170 mGy/h and 3 × 104 mGy/h	HPRT mutations and molecular changes in the HPRT gene	Dose rate effect on cell death; HPRT mutant frequency lower after LDR compared to HDR LDR is as efficient as HDR to produce HPRT deletions	Furuno-Fukushi et al. (1996)
Chinese hamster V79 cells	Underground vs above ground environment (LNGS, Italy) Inside DUL: 10–6 mGy/h	Spontaneous and radiation-induced mutation frequency at the HPRT locus (10 months of continuous culture in different environments)	Increased mutation frequency at the hprt locus before (spontaneous level) and after irradiation with X-ray doses in cultures kept for 10 months underground respect to those above ground Further significant increase of spontaneous HPRT mutant frequency in cells kept for 10 months underground after another 6 months above ground	Fratini et al. (2015)
Drosophila melanogaster (wt Canton S and a mutant strain defective in the excision repair function, (y mei-9a v f y)	X-irradiation Doses: 0.2 and 10 Gy Dose rates: 3 × 103 and 3 × 104 mGy/h	Sex-linked recessive lethal assay using immature sperm	Mutation frequency in the sperm irradiated with a low dose at a low-dose rate significantly lower than that in the sham-irradiated group	Koana et al. (2007)
Human telomere reverse transcriptase (TERT)-immortalised fibroblast	X-irradiation Doses: up to 5 Gy Dose rates: 18 mGy/h and 12 × 104 mGy/h	Mutation induction, PCR analysis of HPRT mutants; survival and micronucleus induction	Less HPRT mutation and less deletions after LDR compared to HDR; smaller size of the deletions after LDR	Nakamura et al. (2005)
Transgenic gpt delta mice	γ-Irradiation Doses and dose rates: 0.75 mGy/h (for 483 consecutive days, i.e.,up to ~ 8.7 Gy, ~ 60 mGy/h (for 2, 4 and 8 days, i.e., up to ~ 11.5 Gy), and ~ 5.5 × 104 mGy/h (for 2, 4 and 8 days, i.e., up to ~ 1 × 104 Gy	Transgenic assay in spleen and liver (mice contain bacterial genes in their genome, which can be assayed for mutations by using bacterial systems)	Mutation induction rate-dependent on the dose rate; it is higher in the spleen than in the liver at the medium-dose rate but similar in the two tissues at the high and low-dose rates. Deletion without any sequence homology at the break point elevated in spleen after HDR irradiation (tissue-specific response)	Okudaira et al. (2010)
S. cerevisiae	Underground vs above ground environment (LNGS, Italy) Inside DUL: 106 mGy/h	Susceptibility to treatments with high doses of a radiomimetic chemical agent (MMS) in terms of mitotic intergenic recombination (after 120 generation, i.e., 1 week)	Higher frequency of recombination in yeast cells grown underground respect to those grown above ground	Satta et al. (1995)
TK6 human lymphoblasts	γ-Irradiation Doses: 0.5, or 1.0 Gy Dose rates: 1.4, 5.0, 15.0, and 30.0 mGy/h	Cell growth, frequency of thymidine kinase (TK) mutants, and of chromosomal aberrations in painted chromosomes 2, 8, and 14	Clear lack of dose rate effect on the frequency of mutants and stable-type chromosomal aberrations (mainly translocations), with a dose rate effect on cell growth and unstable-type aberrations (dicentrics and breaks)	Shakeri Manesh et al. (2014)