Differential effects of genes of the Rb1 signalling pathway on osteosarcoma incidence and latency in alpha-particle irradiated mice.

摘要: Osteosarcoma is the most frequent secondary malignancy following radiotherapy of patients with bilateral retinoblastoma. This suggests that Rb1 tumour suppressor gene might confer genetic susceptibility towards radiation-induced osteosarcoma. To define contribution pathway in multistep process radiation carcinogenesis, we evaluated somatic allelic changes affecting itself as well its upstream regulator p16 murine osteosarcoma induced by 227Th incorporation. distinguish between germline predisposition and effect a 2-hit loss, two mouse models harbouring heterozygote defects were tested for incidence latency irradiation. We could show all tumours arising BALB/c × CBA/CA hybrid mice (wild-type p16) carried loss either (76.5%) or (59%). In none tumours, found concordant retention heterozygosity at both loci. Heterozygote knock-out exhibit significant increase incorporation (22/24 Rb1+/− vs. 2/18 Rb1+/+, p = 4 10−5), without latency. contrast, had no change incidence, but pronounced reduction (LT50% 355 days p16+/− 445 p16+/+, 8 10−3). These data suggest influence early steps osteosarcomagenesis, whereas alterations mainly affect later stages promotion growth.