Modulation by phenethyl isothiocyanate and budesonide of molecular and histopathologic alterations induced by environmental cigarette smoke in mice.
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.
D'Agostini
Francesco
F
Department of Health Sciences, University of Genoa, Genoa, Italy.
Mastracci
Luca
L
Izzotti
Alberto
A
Balansky
Roumen
R
Pennisi
Tanya M
TM
Steele
Vernon E
VE
De Flora
Silvio
S
D000236:Adenoma / Q000209:etiology / Q000517:prevention & control; D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D016588:Anticarcinogenic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D001854:Bone Marrow Cells / Q000187:drug effects / Q000473:pathology; D019819:Budesonide / Q000494:pharmacology / Q000627:therapeutic use*; D002277:Carcinoma / Q000209:etiology / Q000517:prevention & control; D018736:DNA Adducts / Q000032:analysis; D004354:Drug Screening Assays, Antitumor; D004847:Epithelial Cells / Q000187:drug effects / Q000473:pathology; D005260:Female; D017879:Isothiocyanates / Q000494:pharmacology / Q000627:therapeutic use*; D008168:Lung / Q000737:chemistry / Q000187:drug effects; D008171:Lung Diseases / Q000188:drug therapy / Q000473:pathology; D008175:Lung Neoplasms / Q000209:etiology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D011230:Precancerous Conditions / Q000188:drug therapy / Q000473:pathology; D011247:Pregnancy; D013997:Time Factors; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*
D016588:Anticarcinogenic Agents; D018736:DNA Adducts; D017879:Isothiocyanates; D014028:Tobacco Smoke Pollution; D019819:Budesonide; C058305:phenethyl isothiocyanate