Biodosimetry using radiation-induced micronuclei in skin fibroblasts

Abstract

Purpose: We assessed micronuclei in dermal fibroblasts as a local biodosimeter for estimating accidental in vivo radiation exposure.

Materials and methods: Male and female C3H/HeJ and C57Bl6 mice of four age groups (∼11, 36, 60 and 99 weeks) received a single whole body dose of gamma radiation (0–10 Gy) and radiation-induced micronuclei per 1,000 binucleated cells were assessed in skin fibroblasts in their first division after isolation from biopsies taken on days 1 and 7 post irradiation. The method of generalized estimating equations was used for statistical analyses.

Results: Total micronuclei were increased on day 1 in a dose-dependent manner in the range of 1–10 Gy, with no significant attenuation of response between day 1 and day 7 and no significant effect of gender. Between-strain differences were observed with C3H/HeJ mice showing lower background micronuclei and a slightly steeper dose response. Age affected only the background micronuclei (moderate increase with age). The model demonstrated that the assay yields ‘unbiased’ prediction of the dose between 0 and 7 Gy. Within this dose range, the predicted dose was found to be accurate within ±1.5–2 Gy. When the specificity is set to 95%, the assay can distinguish between unexposed and 2 Gy exposed mice with a sensitivity of around 60%. The sensitivity approached 100% when discriminating between unexposed mice and mice receiving doses equal to or greater than 4 Gy. The percentage of binucleated cells with micronuclei was shown to be useful as a simpler and slightly faster substitute for the total micronuclei count.

Conclusion: Micronuclei in dermal fibroblasts isolated up to 1 week after irradiation can be a useful biodosimeter for local dose after accidental radiation exposure.

Keywords:

• micronucleus assay
• skin fibroblasts
• biodosimetry
• radiation
• mice

Acknowledgements

This work was funded in part by the US National Institutes of Health (NIAID-U19 program AI-067733) and in part by the Ontario Ministry of Health and Long Term Care (OMHLTC). The views expressed do not necessarily reflect those of OMHLTC.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.