PO-117 Increased risk of in utero x-ray exposure to mice treated with n-ethyl-n-nitrosourea postnatally

Abstract

Introduction A-bomb survivor study reports that in utero exposure to radiation increases risks of not only childhood cancers but also adult-onset cancers. However, little is known about whether the risk of in utero exposure is influenced by postnatal exposure to other carcinogens. In this study, we examined the lifespan shortening and cancer risk of mice after irradiation in utero and treatment with N -ethyl- N -nitrosourea postnatally. Material and methods Female B6C3F1 mice were either irradiated with 2 Gy X-rays at embryonic day 17 (X-ray alone) or administrated with 125 ppm N -ethyl- N -nitrosourea (ENU) for 4 weeks from 5, 9, or 13 weeks old (ENU alone). Another groups of mice were both exposed to X-rays in utero and administrated with ENU postnatally, i.e., 5, 9, or 13 weeks old (X-rays+ENU). Control group were treated with sham-irradiation and vehicle-only. All mice were analysed for the life-span shortening and tumour spectrum histopathologically at moribund or just after death. Results and discussions The mean lifespan of control mice was 797+/-143 days. In utero X-ray exposure shortened lifespan by 8.5%. The mean lifespan of mice treated with ENU alone at 5, 9 and 13 weeks of age were 366+/-117, 461+/-104, and 475+/-123 days, respectively. In utero exposure shortened lifespan of mice postnatally treated with ENU at 5, 9 and 13 weeks of age by 16.8, 9.0 and 7.5%, respectively, indicating that estimated risk of in utero exposure was enhanced by twofold in mice treated with ENU at juvenile (5 weeks). This enhancement is in part ascribed to acceleration of tumour development such as thymic lymphoma. In contrast, the risk of lifespan shortening after in utero exposure was not influenced by ENU treatment when ENU was treated after adults (9 and 13 weeks). Histopathological examination is now undertaken in order to clarify the tumours whose risk is increased by in utero exposure in control and ENU treated mice. Conclusion The risk of in utreo exposure to X-rays was influenced by postnatal treatment with ENU, which depends on the age of ENU treatment. Increase in risk of in utero exposure by juvenile ENU treatment was ascribed to acceleration of tumours such as thymic lymphoma.