Journal Article

Induction, persistence and modulation of cytogenetic alterations in cells of smoke-exposed mice

Roumen M. Balansky, Francesco D' Agostini and Silvio De Flora

in Carcinogenesis

Volume 20, issue 8, pages 1491-1498
Published in print August 1999 | ISSN: 0143-3334
Published online August 1999 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/20.8.1491
Induction, persistence and modulation of cytogenetic alterations in cells of smoke-exposed mice

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In spite of the major role played by smoking tobacco in the epidemiology of chronic degenerative diseases, it is difficult to mimic the genotoxic and carcinogenic effects of this complex mixture in animal models. We undertook an experimental study evaluating the time-course induction, persistence and modulation of cytogenetic alterations induced in BDF1 mice exposed whole-body to mainstream cigarette smoke. The animals were divided into five groups, including: (i) 72 sham-exposed mice; (ii) 72 mice exposed to smoke for up to 3 weeks; (iii) 72 mice treated daily with the thiol N-acetylcysteine (NAC, 0.5 g/kg body weight) with drinking water; (iv) 72 mice exposed to smoke and treated daily with NAC, starting 5 days before exposure to smoke; and (v) 48 mice exposed to smoke and treated daily with NAC, starting 1 day after discontinuation of exposure to smoke. After 1, 2, 3, 4, 5, 6, 7, 10 and 14 weeks since the start of exposure to cigarette smoke, eight mice per group were killed, and cytogenetic parameters were evaluated. Exposure to smoke induced a high frequency of micronucleated and binucleated (BN) pulmonary alveolar macrophages, which persisted for at least 14 weeks. The frequency of micronuclei increased early in bone marrow polychromatic erythrocytes, but declined to background levels upon discontinuation of exposure to smoke. By comparison, their induction in circulating normochromatic erythrocytes (NCE) was slightly delayed, less intense but still significant, and persisting for an additional 3 weeks. Administration of NAC, throughout duration of the experiment, strongly inhibited the smoke-induced formation of micronuclei in alveolar macrophages and had some transiently significant effect on the induction of BN macrophages. NAC did not significantly decrease the smoke-induced formation of micronuclei in bone marrow cells, whereas it attenuated the formation of micronuclei in peripheral blood NCE. When given after discontinuation of exposure to cigarette smoke, NAC did not affect the cytogenetic alterations but normalized the altered bronchoalveolar lavage cellularity. The present data provide a detailed analysis of time-related cytogenetic alterations in smoke-exposed mice, both in the respiratory tract and at a systemic level, and show the effects of NAC on these parameters and on the pulmonary inflammatory response.

Keywords: BM, bone marrow; BN, binucleated; CA, chromosomal aberrations; CS, cigarette smoke; MN, micronucleated; NAC, N-acetylcysteine; NCE, normochromatic erythrocytes; PAM, pulmonary alveolar macrophages; PCE, polychromatic erythrocytes; PMN, polymorphonucleates; SCE, sister chromatid exchanges

Journal Article.  5875 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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