Molecular and Cytogenetical Alterations Induced by Environmental Cigarette Smoke in Mice Heterozygous for <i>Fhit</i>

Flora, Silvio De; D’Agostini, Francesco; Izzotti, Alberto; Zanesi, Nicola; Croce, Carlo M.; Balansky, Roumen

doi:10.1158/0008-5472.can-06-3882

Cited by 18 publications

(10 citation statements)

References 37 publications

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“…These findings support the conclusions of our previous studies showing the ability of ECS to induce genotoxic damage and other alterations of intermediate biomarkers in various cells, tissues, and organs of rodents exposed in vivo (5,10,21,22,(40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52).…”

Section: Discussionsupporting

confidence: 91%

Modulation by Phenethyl Isothiocyanate and Budesonide of Molecular and Histopathologic Alterations Induced by Environmental Cigarette Smoke in Mice

D’Agostini

Mastracci

Izzotti

et al. 2009

Cancer Prevention Research

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Our discovery that the perinatal period involves nucleotide modifications and gene overexpression in mouse lung prompted us to evaluate whether mice may become more susceptible to cigarette smoke when exposure starts immediately after birth. We previously showed that mainstream cigarette smoke is a quite potent carcinogen in neonatal mice. Further on, we showed that exposure of mice to environmental cigarette smoke (ECS), starting at birth, results in alterations of a variety of intermediate biomarkers. However, after 4 months of exposure to ECS followed by 7 months of recovery in filtered air, the lung tumor yield was rather low. In the present study, we evaluated the protective effects of the glucocorticoid budesonide and of the dietary agent phenethyl isothiocyanate in mice exposed to ECS for 9 months followed by 2 months of recovery. After weanling, the mice exposed to ECS since birth underwent a variety of alterations of molecular and cytogenetical end points, and 11 months after birth, they exhibited significant histopathologic changes, such as pulmonary anthracosis, emphysema, hemorrhagic areas, alveolar bronchiolarization, bronchial hyperplasia, and tumors, both benign and malignant. The carcinogenic response was less evident in dams exposed to ECS under identical conditions. Both phenethyl isothiocyanate and budesonide, administered daily with the diet after weanling, attenuated several alterations of ECS-related biomarkers and moderately protected the lungs from histopathologic alterations, including tumors. Thus, although not as efficiently as the bioassay in mainstream cigarette smoke-exposed mice, the model in neonatal mice is suitable to evaluate both ECS carcinogenicity and its modulation by chemopreventive agents.

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Section: Discussionsupporting

confidence: 91%

Modulation by Phenethyl Isothiocyanate and Budesonide of Molecular and Histopathologic Alterations Induced by Environmental Cigarette Smoke in Mice

D’Agostini

Mastracci

Izzotti

et al. 2009

Cancer Prevention Research

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“…Yet, the presence of two or more nuclei must be considered as the result of a cytokinesis block after completion of nuclear division, resulting in disruption of the cellular skeleton and formation of supranumerary centrosomes and multipolar mitotic spindles (Stavropoulou et al, 2005;Shi and King, 2005;Thomas et al, 2009). Tobacco smoke is a potent inducer of BNC in rodent pulmonary alveolar macrophages, as demonstrated in several studies performed by our group , 2007Balansky et al, 1993Balansky et al, , 1999Balansky et al, , 2000Balansky et al, , 2003Izzotti et al, 2001), as well as by others (Matulionis and Traurig, 1977;Talbot et al, 1987;Hornby and Kellington, 1990). A smoke-related increase of BNC in the oral mucosa of smokers was also reported by Nersesyan et al (2011).…”

Section: Discussionmentioning

confidence: 80%

Cytogenetic analysis of gingival epithelial cells, as related to smoking habits and occurrence of periodontal disease

D’Agostini¹,

Calcagno²,

Micale³

et al. 2013

International Journal of Hygiene and Environmental Health

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“…In a separate report, D'Agostini et al [41] exposed wild type and FHIT +/− rodents to environmental cigarette smoke (ECS). Evaluation of FHIT expression in the respiratory tract after 14 days of exposure to ECS revealed unequivocal evidence that FHIT is an early, critical target in smoke-related carcinogenesis [41], but heterozygosity for FHIT does not seem to confer an increased susceptibility of mice in terms of early biomarkers like apoptosis, cell proliferation, bulky DNA adducts in the lung, and various cytogenetical damages [42]. …”

Section: Fhitmentioning

confidence: 99%

Common Fragile Site Tumor Suppressor Genes and Corresponding MouseModels of Cancer

Drusco

Pekarsky

Costinean

et al. 2010

BioMed Research International

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Chromosomal common fragile sites (CFSs) are specific mammalian genomic regions that show an increased frequency of gaps and breaks when cells are exposed to replication stress in vitro. CFSs are also consistently involved in chromosomal abnormalities in vivo related to cancer. Interestingly, several CFSs contain one or more tumor suppressor genes whose structure and function are often affected by chromosomal fragility. The two most active fragile sites in the human genome are FRA3B and FRA16D where the tumor suppressor genes FHIT and WWOX are located, respectively. The best approach to study tumorigenic effects of altered tumor suppressors located at CFSs in vivo is to generate mouse models in which these genes are inactivated. This paper summarizes our present knowledge on mouse models of cancer generated by knocking out tumor suppressors of CFS.

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Molecular and Cytogenetical Alterations Induced by Environmental Cigarette Smoke in Mice Heterozygous for Fhit

Abstract: Previous studies in humans and animal models provided evidence that the Fhit gene is an early target for cigarette smoke. We compared the induction of a variety of molecular and cytogenetical alterations in B6

Cited by 18 publications

References 37 publications

Modulation by Phenethyl Isothiocyanate and Budesonide of Molecular and Histopathologic Alterations Induced by Environmental Cigarette Smoke in Mice

Modulation by Phenethyl Isothiocyanate and Budesonide of Molecular and Histopathologic Alterations Induced by Environmental Cigarette Smoke in Mice

Cytogenetic analysis of gingival epithelial cells, as related to smoking habits and occurrence of periodontal disease

Common Fragile Site Tumor Suppressor Genes and Corresponding MouseModels of Cancer

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