The Transgenerational Mutagenic and Carcinogenic Effect of Ionising Radiation*

Ildikó Klementis, Katalin Lumniczky, Enikö Kis, Tünde Szatmári, Sára Antal, and Géza Sáfrány

Department of Molecular and Tumour Radiobiology, National Research Institute for Radiobiology and Radiohygiene,
József Fodor National Center for Public Health, Budapest, Hungary

Corresponding author: Géza Sáfrány
    NCPH - National Research Institute for Radiobiology and Radiohygiene
    P.O.Box 101
    H-1221 Budapest, Hungary
    Telephone: +36 1 482-2010
    Fax number: +36 1 482-2010
    E-mail: safrany@hp.osski.hu

CEJOEM 2004, Vol.10. No.3.: 235–245


* Edited version of the paper delivered at the 33th Annual Meeting
of the European Society for Radiation Biology, Budapest, August 25–28, 2004


Key words:
Paternal irradiation, genomic instability, minisatellite mutations, cancer incidence


Abstract:
Ionising radiation can induce mutations both in somatic and germ line cells. Mutations in germ cells might be inherited by the next generations and the inherited mutations may induce cancer in the population affected. Exposure of the affected population to a second environmental carcinogen might further increase the cancer incidence. This possibility was studied in a murine experimental model system.
    Male mice were irradiated with either 60Co-g or fission neutron radiation. The irradiated mice were mated with unirradiated females during the 1st, 3rd, and 11th weeks after irradiation. First we studied the effect of paternal irradiation on mating efficiency and on the litter size. When mating was performed during the first week after irradiation (spermatozoa stage), only high dose neutron radiation caused a significant decrease in litter size. The male germ cells were the most sensitive to irradiation at the spermatid stage (third week after irradiation), when a dose-dependent decrease in the litter size was detected. If mating was performed during the eleventh week after irradiation (the sperms were irradiated at the spermatogonium stage) the litter size returned to the normal level. Decreased mating efficiency (14–66%) was detected after high dose g (3 Gy) and neutron (1.5–2.0 Gy) radiations, when the cells were irradiated in the spermatid and spermatogonium stages.
    To investigate paternal irradiation induced mutations in the offspring, DNA was isolated from tail pieces of F1 mice. The number of minisatellite mutations was determined by Southern blot hybridization to mouse minisatellite DNA probe M and Pc-1. Exposure to 2 Gy neutron irradiations at the spermatozoa stage doubled the mutation incidence in the offspring. When the exposure occurred at the spermatid stage the mutation rates increased in a dose-dependent manner both after neutron and g radiations. The highest mutation rate was detected after exposure to 2 Gy neutron radiation (4-fold increase). Exposure at the spermatogonium stage also increased the mutation rate.
    The cancer incidence after paternal irradiation was also followed in the offspring. We have observed a dose-dependent increase in tumour incidence after irradiation at the spermatid stage. To investigate the potential synergistic effect of a second environmental carcinogen, paternally irradiated mice were treated with a chemical carcinogen ethylnitrosourea (ENU) on the 15–18th prenatal day; it further increased the cancer incidence.
    In conclusion, paternal irradiation might increase the minisatellite mutation rates in the F1 offspring and the cancer incidence could also be enhanced.


Received: 25 October 2004
Accepted: 29 October 2004

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