title: Co-operative effects of thoracic X-ray irradiation and N-nitrosobis(2-hydroxypropyl) amine administration on lung tumorigenesis in neonatal, juvenile and adult Wistar rats.
abstract: Assessment of risks associated with childhood exposure to ionizing radiation when combined with chemical carcinogens is of great importance. We studied the age-dependence of the effect of combined exposure to ionizing radiation (IR) and a chemical carcinogen on lung carcinogenesis. 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 N-nitrosobis(2-hydroxypropyl)amine (BHP) (1g/kg body weight) 1 week after X-ray exposure or at 23 weeks of age. Rats were terminated 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, although this was not statistically significant, 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 effective than that at late-life stage (22 weeks irradiation); (iii) combined exposure preferentially enhanced malignant transformation; (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; (v) adenomas and adenocarcinomas induced by X-ray and/or BHP originated from surfactant apoprotein A-positive alveolar type II cells; and (vi), extracellular signal-regulated kinase pathway activation was observed in half the adenocarcinomas, regardless of the exposure schedule. In conclusion, combined exposure may enhance lung tumorigenesis more synergistically at early-life stage (5 weeks of age) than later-life stage.
authors: Radiobiology for Children's Health Program, Research Center for Radiation Protection, National Institute of Radiological Sciences, Anagawa 4-9-1, Inage-ku, Chiba 263-8555, Japan. k_iwata@nirs.go.jp
authors: Ken-ichi
authors: K
authors: Iwata
authors: Yutaka
authors: Y
authors: Yamada
authors: Akifumi
authors: A
authors: Nakata
authors: Yoichi
authors: Y
authors: Oghiso
authors: Shusuke
authors: S
authors: Tani
authors: Kazutaka
authors: K
authors: Doi
authors: Takamitsu
authors: T
authors: Morioka
authors: Benjamin J
authors: BJ
authors: Blyth
authors: Mayumi
authors: M
authors: Nishimura
authors: Shizuko
authors: S
authors: Kakinuma
authors: Yoshiya
authors: Y
authors: Shimada
mesh_terms: D000230:Adenocarcinoma / Q000139:chemically induced / Q000209:etiology / Q000473:pathology; D000236:Adenoma / Q000139:chemically induced / Q000209:etiology; D000375:Aging / Q000187:drug effects / Q000528:radiation effects; D000818:Animals; D000831:Animals, Newborn; D002273:Carcinogens / Q000633:toxicity*; D002471:Cell Transformation, Neoplastic / Q000187:drug effects* / Q000473:pathology / Q000528:radiation effects*; D005260:Female; D008175:Lung Neoplasms / Q000139:chemically induced* / Q000209:etiology / Q000473:pathology; D009381:Neoplasms, Radiation-Induced / Q000139:chemically induced* / Q000473:pathology; D009602:Nitrosamines / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D013909:Thorax / Q000187:drug effects* / Q000473:pathology / Q000528:radiation effects*
chemical_list: D002273:Carcinogens; D009602:Nitrosamines; C012457:diisopropanolnitrosamine