Abstract
Mortality in life-span studies of radiation carcinogenesis is a useful endpoint for risk assessment of radiation. Although various neoplasm have been reported in life-span studies, their biological profiles as well as nomenclature remain to be undetermined except some tumors which are induced by radiation. We investigated immunohistochemical profiles in the solid tumors (formalin-fixed and paraffin-embedded samples) observed in life-span studies using female B6C3F1 mice exposed to carbon ions and X-rays and control ones. We focused on reaction to proliferative cell nuclear antigen (PCNA) and p53 antibodies. The types of tumors were 10 well-differentiated adenocarcinomas in the lung, 14 granulosa cell tumors (GCTs), 4 ovarian tubular adenomas, 1 ovarian cancer, 3 endometrial adenocarcinomas, 6 fibrosarcomas, 5 angiosarcomas, 4 leiomyosarcomas, 2 malignant schwannomas, 1 rabdomyosarcoma and 1 histiocytic sarcoma. The lung, uterine tumors and GCTs were obtained from the animals exposed to the radiation. As a result, the ovarian, uterine and soft part tumors were strongly positive to PCNA, and some of them were often metastasized to the lung or other sites. Less PCNA positive cells were detected in most of the lung cancers. Interestingly, a half of GCTs showed positive reaction to p53, and negative to p21 and MDM2 antibodies. These results suggest the ovarian, uterine and soft tissue tumors have high proliferative cell activity, which might be related with metastasis, but growth of the lung tumors have low one. Expression of P53 might be a key process of GCT tumorigenesis.
