Presentation The combined effects of X-rays and N-nitrosobis (2-hydroxypropyl) amine on lung carcinogenesis in neonatal, juvenile and adult Wistar rats.

山田, 裕  ,  岩田, 健一  ,  山崎, 隼輔  ,  谷, 修祐  ,  土居, 主尚  ,  森岡, 孝満  ,  Benjamin, Blyth  ,  西村, まゆみ  ,  柿沼, 志津子  ,  島田, 義也

Numerous physical, chemical and biological carcinogens are found in the environment; and, quantifying the effects of combined exposure to different carcinogens is a priority for ensuring human health. The lung can be easily exposed to inhaled carcinogens, with tobacco smoke the leading cause of lung cancer. Epidemiological studies indicate that children are more susceptible to the carcinogens in tobacco smoke than adults. The increasing use of diagnostic and therapeutic radiation in children is another source of growing concern about lung cancer risk, with CT scans and radiotherapy representing the highest sources of dose and risk. However, little is known of the combined lung cancer risk associated with exposure to both ionizing radiation and chemical carcinogens, or how the risk changes with age at exposure. To investigate this further, female 1-, 5-, and 22-week-old Wistar rats were locally irradiated on the thorax with X-rays (3.18 Gy) and/or were injected intraperitoneally with the alkylating agent N-nitrosobis (2-hydroxypropyl) amine (BHP) (1 g/kg body weight) 1 week after X-ray exposure or at 23 weeks of age, and euthanised at 90 weeks of age. We found that: (i) the incidence of lung tumors (adenoma and adenocarcinoma) increased slightly as a function of age at X-ray exposure, while the incidence induced by BHP decreased with increasing age at administration; (ii) combined exposure to X-rays at 5 or 22 weeks with BHP 1 week later enhanced the tumor incidence, and the effect at early-life stage (5 weeks irradiation) was more pronounced than that at late-life stage (22 weeks irradiation); (iii) combined exposure preferentially enhanced malignant transformation and adenocarcinoma; (iv) although a longer interval between the X-ray and BHP treatments reduced the combined effect, risks of early-life irradiation at 1 or 5 weeks of age lasted into adulthood. In summary, the combined treatment enhanced cancer incidence more synergistically at earlier-life stage (5 weeks) than later-life stage (22 weeks) and the carcinogenic events of early-life irradiation lasted into adulthood and were enhanced by BHP, suggesting an unrecognized increased risk following combined exposures in children.

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