Susceptibility to radiation-induced leukaemia/lymphoma is genetically separable from sensitivity to radiation-induced genomic instability

Abstract

Purpose : To determine whether there is a relationship between the genetics underlying the susceptibility to radiation-induced leukaemia in CBA/H (acute myeloid leukaemia, AML) and C57BL/6 (thymic lymphoma, TL) mice, and the genetics underlying the sensitivity of CBA/H (sensitive) and C57BL/6 (resistant) mice to radiation-induced chromosomal instability. Materials and methods : CBA/H, (CBA/H ×C57BL/6)F 1, F 1 ×CBA/H, F 1 ×C57BL/6 and F 1 ×F 1 mice were exposed to a single acute dose of 3.0 Gy X-rays. AML and TL were diagnosed over the subsequent 30 months. Results : There was no statistically significant difference in the incidence of AML in F 1, F 1 ×F 1, F 1 ×CBA/H and F 1 ×C57BL/6 mice, which was ~50% that in CBA/H mice. AML susceptibility is therefore a dominant polygenic trait, and both susceptibility and resistance (variable penetrance) CBA/H and C57BL/6 loci are involved. The incidence of TL in the F 1 and F 1 ×CBA/H mice was negligible, indicating that TL susceptibility is a recessive trait. As the TL incidence in the F 1 ×C57BL/6 mice was about half that in C57BL/6 mice, one recessive locus is probably involved. Conclusions : AML susceptibility in CBA/H mice is a dominant trait in contrast to the recessive inheritance of CBA/H sensitivity to radiation-induced chromosomal instability. TL-susceptibility in C57BL/6 is a recessive trait in contrast to the dominant inheritance of C57BL/6 resistance to radiation-induced chromosomal instability.