Radiation-induced myeloid leukemia in C3H/He mice and the effect of prednisolone acetate on leukemogenesis.
ABSTRACT We found that the incidence of spontaneous myeloid leukemia in C3H/He male mice was less than 1%, but it could be increased considerably by total-body X irradiation. The induction of myeloid leukemia was seen to increase after doses from 0.47 Gy (3%) to 2.84 Gy (23.9%), and then decrease after a dose of 4.73 Gy (13.6%). The administration of prednisolone acetate (synthesized glucocorticoid) after irradiation resulted in a significant increase in the incidence of myeloid leukemia from 23.9 to 38.5% after a dose of 2.84 Gy; however, corticosterone, a glucocorticoid secreted by cells, did not have such an enhancing effect.
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ABSTRACT: As the number of cancer survivors treated with radiation as a part of their therapy regimen is constantly increasing, so is concern about radiation-induced cancers. This increases the need for therapeutic and mitigating agents against secondary neoplasias. Development and efficacy testing of these agents requires not only extensive in vitro assessment, but also a set of reliable animal models of radiation-induced carcinogenesis. The laboratory mouse (Mus musculus) remains one of the best animal model systems for cancer research due to its molecular and physiological similarities to man, small size, ease of breeding in captivity and a fully sequenced genome. This work reviews relevant M. musculus inbred and F(1 )hybrid animal models and methodologies of induction of radiation-induced leukemia, thymic lymphoma, breast, and lung cancer in these models. Where available, the associated molecular pathologies are also included.International Journal of Environmental Research and Public Health 01/2012; 10(1):107-43. · 2.00 Impact Factor
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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 (3.18Gy) and/or were injected intraperitoneally with N-nitrosobis(2-hydroxypropyl)amine (BHP) (1g/kg body weight) 1week after X-ray exposure or at 23weeks of age. Rats were sacrificed at 90weeks 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 stastically not significant. On the other hand, the incidence by the BHP decreased with increasing age at the administration; (ii) combined exposure to X-rays at 5 or 22weeks with BHP 1week later enhanced the tumor incidence, and the effect at early-life stage (5weeks irradiation) was more effective than that at late-life stage (22weeks irradiation); (iii) that 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 5weeks 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 (5weeks of age) than later-life stage.Toxicology and Applied Pharmacology 01/2013; · 3.98 Impact Factor
- Blood Cancer Journal 01/2013; 3:e161. · 1.40 Impact Factor