Differential carcinogenicity of cigarette smoke in mice exposed either transplacentally, early in life or in adulthood
Differential carcinogenicity of cigarette smoke in mice exposed either transplacentally, early in life or in adulthood
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DOI：
10.1002/ijc.26103
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发表时间：
2012-03-01
影响因子：
6.4
通讯作者：
De Flora, Silvio
中科院分区：
文献类型：
--
作者：
Balansky, Roumen;Ganchev, Gancho;De Flora, Silvio
香烟烟雾（CS）在人类癌症流行病学中起着主导作用。但在实验动物中很难重现其致癌性。最近，我们发现CS在小鼠出生后不久开始暴露时成为一种强有力的致癌物质。在我们的研究中，我们比较评估了不同年龄的小鼠对主流CS的致癌反应。新生小鼠每天暴露于CS，持续4个月，出生后12小时内开始，并在8个月时处死。成年小鼠暴露相同的时间段（37个月），并在11个月时处死。其他小鼠经胎盘暴露或经胎盘暴露和生命早期暴露。共使用了351只新生小鼠和80只成年Swiss H小鼠。CS根据年龄的不同而引起不同程度的肺气肿、支气管和肺泡上皮增生、血管增生、肺血管瘤和微腺瘤以及肝脏实质变性。仅在生命早期暴露于CS的小鼠中观察到肾脏的组织学改变。在暴露于该物质的小鼠体内检测到肺腺瘤和各种组织病理学性质的恶性肿瘤，但在成年小鼠体内未检测到。出生后8个月，经胎盘CS诱导后代形成肺腺瘤。妊娠期暴露可减弱出生后诱导的CS相关肺泡上皮增生。总之，对CS的致癌反应因发育阶段而异。早期出生后的生活和产前生活是特别危险的，为以后的发展CS相关的肿瘤。
Cigarette smoke (CS) plays a dominant role in the epidemiology of human cancer. However, it is difficult to reproduce its carcinogenicity in laboratory animals. Recently, we showed that CS becomes a potent carcinogen in mice when exposure starts soon after birth. In our study, we comparatively evaluated the carcinogenic response to mainstream CS in mice at different ages. Neonatal mice were exposed daily for 4 months to CS, starting within 12 hr after birth, and sacrificed at 8 months. Adult mice were exposed for the same time period (37 months) and sacrificed at 11 months. Other mice were exposed transplacentally or both transplacentally and early in life. A total of 351 neonatal mice and 80 adult Swiss H mice were used. With varying intensity depending on age, CS induced pulmonary emphysema, bronchial and alveolar epithelial hyperplasia, blood vessel proliferation and hemangiomas and microadenomas in lung as well as parenchymal degeneration of liver. Histopathological alterations of kidney were only observed in mice exposed to CS early in life. Lung adenomas and malignant tumors of various histopathological nature were detected in neonatally exposed mice but not in adults. Transplacental CS induced the formation of lung adenomas in the offspring 8 months after birth. Previous exposure during pregnancy attenuated CS-related alveolar epithelial hyperplasia induced after birth. In conclusion, the carcinogenic response to CS varies depending on the developmental stage. The early postnatal life and the prenatal life are particularly at risk for the later development of CS-related tumors.