Enhancing Effects of N-Nitrosobis (2-Hydroxypropyl) Amine on Pulmonary Tumorigenesis in Juvenile and Adult Wistar Rats after Thoracic Irradiation with X rays

Abstract

Combined effects of radiation and chemical carcinogen on pulmonary tumorigenesis in juvenile and adult animals were investigated. Female, 5- and 22-week-old Wistar rats were locally irradiated on the thorax with 3.18 Gy of X-ray, and/or then N-nitrosobis (2-hydroxypropyl) amine (BHPN; 1g/kg body weight) was intraperitoneally injected at intervals of a week or 18 weeks. While control animals still survived at 90 weeks of age when all animals were sacrificed, the administration of BHPN to both 6- and 23-week-old rats resulted in survival reduction due to kidney, brain and ovary tumors. Single irradiation or BHPN alone increased incidence of lung tumors, although most of tumors were benign adenomas. The tumorigenic effects in rats given a combined treatment with irradiation and BHPN were synergistic, and lung carcinomas increased in groups irradiated at 5 and 22 weeks of age. Immunohistochemical staining showed SP-A- and CC-10-positive cells localized in both adenomas and adenocarcinomas induced by thoracic irradiation and/or BHPN administration, suggesting that the lung tumors appear to be mostly derived from alveolar type II cells and Clala cells. These results indicate that X-rays and BHPN affect the same type of target epithelial cells, and posterior treatment with BHPN synergistically enhances radiation-induced lung tumors in juvenile and adult rats.