In spite of the outstanding role of tobacco smoking in human carcinogenesis, it is difficult to reproduce its effects in experimental animals. Based on the knowledge that a variety of mechanisms account for a higher susceptibility to carcinogens early in life, we have developed a murine model in which mainstream cigarette smoke becomes convincingly carcinogenic. The standard model involves exposure to smoke for 4 months, starting after birth, followed by an additional 3-4 months in filtered air. We evaluated herein the time- and dose-dependent response, at 7.5 months of life, of Swiss H mice that had been exposed to smoke for either 1, 2, or 4 months after birth. A one-month exposure, corresponding to a period of intense alveolarization, was sufficient to induce most inflammatory, degenerative, and preneoplastic pulmonary lesions, including emphysema and alveolar epithelial hyperplasia, blood vessel proliferation and hemangiomas, reflecting an early proangiogenic role of smoking, and microadenomas bearing ki-67-positive proliferating cells as well as urinary bladder epithelial hyperplasia. Two months of exposure were needed to induce pulmonary adenomas and urinary bladder papillomas in males only, which highlights a protective role of estrogens in urinary bladder carcinogenesis. Four months, which in humans would correspond to the postnatal period, puberty, adolescence, and early adulthood, were needed to induce other lesions, including tubular epithelial hyperplasia of kidney, bronchial epithelial hyperplasia, and especially pulmonary malignant tumors. These findings highlight the concept that preneoplastic and neoplastic lesions occurring in adulthood can be induced by exposure to smoke early in life.
|Titolo:||Carcinogenic response and other histopathological alterations in mice exposed to cigarette smoke for varying time periods after birth|
|Data di pubblicazione:||2018|
|Appare nelle tipologie:||01.01 - Articolo su rivista|
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