Irradiation of rainbow trout at early life stages results in legacy effects in adults CARMEL MOTHERSILL, RICHARD W. SMITH, ROHIN SAROYA, JANET DENBEIGH, BRITNI ROWE, LAURA BANEVICIUS, RACHEL TIMMINS, RICHARD MOCCIA, & COLIN B. SEYMOUR Department of Medical Physics and Applied Radiation Sciences, McMaster University, Hamilton, Ontario, Canada (Received 30 December 2009; Revised 9 April 2010; Accepted 11 April 2010) Abstract Purpose: Communication of signals from irradiated to non-irradiated fish has been demonstrated by our group for adults. Major questions are however, whether the effects persist for significant lengths of time (meaning there are memories or legacies of the exposure) and whether they are induced in young animals or very early stages in the life cycle. Methods: To address these questions we used a reporter cell clonogenic bioassay to detect the effects of radiation exposure and of ‘bystander’ signals, emitted from irradiated fish, on non-irradiated fish. The legacy of radiation exposure or receipt of bystander signals was investigated in rainbow trout irradiated as eggs at 48 h, eyed eggs at one month, yolk sac larvae (YSL) at two months and juveniles at three months after fertilisation. The irradiated and bystander fish together with shams and unhandled husbandry controls were grown on in a hatchery and examined as they reached each of the remaining life stages. They were also re-examined as one-year-olds with and without further irradiation and finally examined as sexually mature two-year-olds. Results: The data indicate a clear legacy effect of irradiation at any early life stage in the adult fish. Conclusion: The data suggest that bystander signals can be transmitted in vivo and once induced are persistent during the animals’ lifespan. Keywords: low radiation dose effects, bystander effects, adaptive response, fish radiobiology, life stage effects Introduction Solid experimental evidence for ‘bystander effects’ in various guises has been available for almost a century. Murphy and Morton (1915) described damaging factors in the blood of irradiated patients which could affect tumour growth if injected into rats. Since then, there has been sporadic interest in clastogenic factors (Parsons is 1954, Liu et al. 1999, Mothersill and Seymour 2001b, 2006a, Morgan 2003b) which are factors persisting in the blood of irradiated organisms including humans which cause chromosome damage in the same organism or in cell cultures or animal models. The current interest dates from the mid-1980s when several laboratories reported persistent and delayed effects of both low and high Linear Energy Transfer (LET) exposure in surviving progeny of irradiated cells and non- irradiated cells receiving signals from irradiated cells (Seymour and Mothersill 1997, Lyng et al. 2002, Lorimore et al. 2003, Chapman et al. 2008, Coates et al. 2008, Postiglione et al. 2009). Because they were caused by very low dose exposures, these phenomena of genomic (chromosomal) instability and bystander effects became twin pillars supporting the new ‘non-targeted effects’ component of radia- tion damage which is causing concern in radiation risk assessment circles (Biological Effects of Ionising Radiation [BEIR] 2006). While the experimental evidence for these effects is prolific, two problems exist: (i) No one has yet been able to determine the nature of the factor(s) which maintain the unstable state or transmit the information from one irradiated cell to another unirradiated cell; and (ii) no one has any idea of how this communication impacts on radiation risk. The current state-of-the-art in this complex field is reviewed in many papers – for example, Morgan (2003a) and Schwartz (2007). Key Correspondence: Prof. Carmel Mothersill, Department of Medical Physics and Applied Radiation Sciences, McMaster University, Hamilton, Ontario, Canada, L8S 4K1. Tel: þ905 525 9140 ext 26227. Fax: þ905 522 5982. E-mail: mothers@mcmaster.ca Int. J. Radiat. Biol., Vol. 86, No. 10, October 2010, pp. 817–828 ISSN 0955-3002 print/ISSN 1362-3095 online Ó 2010 Informa UK, Ltd. DOI: 10.3109/09553002.2010.486018 Int J Radiat Biol Downloaded from informahealthcare.com by 206.132.59.63 on 11/20/10 For personal use only.