Induction of a germline mutation at a hypervariable mouse minisatellite locus by 252Cf radiation

Area of Science:

• Radiation biology
• Genetics
• Molecular toxicology

Background:

• Minisatellite loci are prone to spontaneous mutations.
• Radiation exposure is a known mutagen.
• Understanding radiation-induced germline mutations is crucial for risk assessment.

Purpose of the Study:

• To investigate the germline mutation frequency at the Ms6hm locus in mice exposed to 252Cf radiation.
• To determine the relative biological effectiveness (RBE) of 252Cf neutrons compared to gamma rays for inducing mutations.

Main Methods:

• Male C3H/HeN mice were exposed to varying doses of 252Cf radiation (0.35, 0.7, 1.02 Gy).
• Exposed males were mated with unirradiated C57BL/6N females.
• F1 offspring were analyzed for germline mutations at the paternally derived minisatellite locus Ms6hm.

Main Results:

• Spontaneous mutation frequency at the Ms6hm locus was 8.4%.
• 252Cf radiation significantly elevated mutation frequencies in a dose-dependent manner.
• Spermatid stage germ cells exhibited the highest sensitivity to 252Cf radiation, with mutation frequencies reaching 26% at 0.7 Gy.

Conclusions:

• 252Cf radiation is a potent inducer of germline mutations in mice.
• The RBE of 252Cf neutrons for minisatellite mutation induction varied by germ cell stage, with values ranging from 2.6 to 6.5.
• These findings highlight the genotoxic potential of mixed neutron-gamma radiation sources.