Abstract
The mean cause of lung cancer is tobacco, which contains numerous alkylating agents. Recently, increase in the chest CT, especially pediatric CT, is also paid rapid attention for the future risk of lung cancer. Therefore, it is a great concern about the risk of lung cancer by childhood exposure of ionizing radiation followed by adulthood exposure to lung carcinogenic chemicals. We examined combined effects of X-rays and an alkylating agent, N-nitrosobis(2-hydroxypropyl)amine (BHP), on pulmonary tumorigenesis in juvenile and adult rats. Female 1-, 5- and 22-week-old Wistar rats were irradiated locally on the thorax with X-rays (3.18 Gy), and/or were given BHP (1 g/kg body weight) intraperitoneally 1 week after each X-rays or 23 weeks of age, and sacrificed at 90 weeks of age.
We found that (i) the induction of lung tumors (both adenoma and carcinoma) increased as a function of age at X-ray-exposure, but decreased at BHP administration, (ii) combined effect of X rays, either exposure at 1, 5 or 22 weeks of age, with BHP at 23 weeks of age induced adenoma and carcinoma in an additive and synergistic fashion, respectively, (iii) the longer interval between two treatments reduced the carcinogenic effects.
Immunohistochemical analysis indicated that most of tumors were originated from SP-A-positive alveolar type II cells and that activation of ERK pathway was limited in this rat model.
In conclusion, the combined effect of X rays with adulthood exposure to BHP on lung tumorigenesis, especially malignant carcinomas, was manifested in a synergistic manners, and the carcinogenic events of juvenile exposure lasted up to adult stage.
