D'Agostini Francesco, Balansky Roumen, Steele Vernon E, Ganchev Gancho, Pesce Carlo, De Flora Silvio
Department of Health Sciences, University of Genoa, Genoa, Italy.
Int J Cancer. 2008 Dec 1;123(11):2497-502. doi: 10.1002/ijc.23836.
It is difficult to reproduce the carcinogenicity of cigarette smoke (CS) in animal models. Recently, we showed that exposure of mice to mainstream CS (MCS) for 120 days, starting immediately after birth, resulted in an early and potent carcinogenic response. In parallel, we implemented studies evaluating intermediate biomarkers and tumors in mice exposed to environmental CS (ECS). To this purpose, we used 263 newborn CD-1 mice born from 27 dams. The whole-body exposure to ECS for 120 days, starting within 12 hr after birth, resulted in an early appearance of preneoplastic lesions in lung, which however tended to attenuate after discontinuing exposure. When the experiment was stopped, after 330 days, the number of lung adenomas was higher in ECS-exposed mice as compared to sham-exposed mice, but such increase was statistically significant only in mice co-exposed to smoke and halogen light mimicking solar irradiation. Moreover, exposure to ECS produced extensive histopathological changes, mainly parenchymatous degeneration, in liver. The alterations produced in both lung and liver require that exposure to ECS starts immediately after birth, no effect being observed when exposure started 8 days later. In contrast, induction by ECS of alterations in the urinary tract, such as microadenomas and adenomas in renal pelvis and kidney, papillary hyperplasia of urothelium, and urinary bladder papillomas, were unrelated to the exposure time after birth. The results obtained with ECS cannot be directly compared to those previously obtained with MCS, since the latter involved shorter daily exposures to more massive CS doses.
在动物模型中重现香烟烟雾(CS)的致癌性很困难。最近,我们发现,从出生后立即开始让小鼠暴露于主流CS(MCS)120天,会导致早期且强烈的致癌反应。同时,我们开展了研究,评估暴露于环境CS(ECS)的小鼠体内的中间生物标志物和肿瘤情况。为此,我们使用了由27只母鼠所生的263只新生CD-1小鼠。从出生后12小时内开始,让小鼠全身暴露于ECS 120天,会导致肺部早期出现癌前病变,不过在停止暴露后这些病变往往会减轻。在330天后实验结束时,与假暴露小鼠相比,暴露于ECS的小鼠肺部腺瘤数量更多,但这种增加仅在同时暴露于烟雾和模拟太阳辐射的卤素光的小鼠中具有统计学意义。此外,暴露于ECS会使肝脏产生广泛的组织病理学变化,主要是实质变性。肺和肝脏中产生的改变都要求在出生后立即开始暴露于ECS,若在出生8天后开始暴露则未观察到任何影响。相比之下,ECS诱发的泌尿系统改变,如肾盂和肾脏中的微腺瘤和腺瘤、尿路上皮乳头增生以及膀胱乳头状瘤,与出生后的暴露时间无关。用ECS获得的结果无法直接与之前用MCS获得的结果进行比较,因为后者涉及每天较短时间暴露于更大剂量的CS。