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Titolo:
Formation and persistence of nucleotide alterations in rats exposed whole-body to environmental cigarette smoke
Autore:
Izzotti, A; Bagnasco, M; DAgostini, F; Cartiglia, C; Lubet, RA; Kelloff, GJ; De Flora, S;
Indirizzi:
Univ Genoa, Sect Hyg & Prevent Med, Dept Hlth Sci, I-16132 Genoa, Italy Univ Genoa Genoa Italy I-16132 Med, Dept Hlth Sci, I-16132 Genoa, Italy NCI, Rockville, MD 20892 USA NCI Rockville MD USA 20892NCI, Rockville, MD 20892 USA
Titolo Testata:
CARCINOGENESIS
fascicolo: 8, volume: 20, anno: 1999,
pagine: 1499 - 1505
SICI:
0143-3334(199908)20:8<1499:FAPONA>2.0.ZU;2-X
Fonte:
ISI
Lingua:
ENG
Soggetto:
CARCINOGEN-DNA ADDUCTS; HYDROCARBON HYDROXYLASE-ACTIVITY; PULMONARY ALVEOLAR MACROPHAGES; CHRONIC DEGENERATIVE DISEASES; N-ACETYLCYSTEINE; TOBACCO-SMOKE; LUNG; TISSUES; GLUTATHIONE; ASSAY;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
51
Recensione:
Indirizzi per estratti:
Indirizzo: De Flora, S Univ Genoa, Sect Hyg & Prevent Med, Dept Hlth Sci, Via A Pastore 1, I-16132 Genoa, Italy Univ Genoa Via A Pastore 1 Genoa Italy I-16132 2 Genoa, Italy
Citazione:
A. Izzotti et al., "Formation and persistence of nucleotide alterations in rats exposed whole-body to environmental cigarette smoke", CARCINOGENE, 20(8), 1999, pp. 1499-1505

Abstract

The assessment of pathological effects produced by environmental tobacco smoke in humans is controversial in epidemiological studies, On the other hand, animal models are poorly sensitive to smoke carcinogenicity, We designed an experimental study assessing the tissue-selective formation and persistence of DNA adducts in smoke-exposed rats. Sprague-Dawley rats were exposed for 6 h per day, 5 days per week, to environmental smoke resulting from amixture of sidestream and mainstream smoke generated from Kentucky 2R1 reference cigarettes. The total particulate matter was in the range of 73-93 mg/m(3), DNA adducts were measured by P-32-postlabelling in rat organs (lung, heart, liver, bladder and testis), tissues (dissected tracheal epithelium) and cells [isolated bronchoalveolar lavage (BAL) cells]. A time-related increase of P-32-post-labelled DNA modifications was detectable by autoradiography, in the form of massive diagonal radioactive zones and individual spots. Top levels were reached after 4-5 weeks of exposure. The ratio of smoke-induced DNA adducts to the background levels detected in sham-exposed rats was 11.2 in the tracheal epithelium, 10.4 in BAL cells, 7.3 in the heart,6.3 in the lung, 5.1 in the bladder, 1.9 in the testis and 1.1 in the liver. Appearance of DNA adducts in the lung was also revealed by synchronous fluorescence spectrophotometry, Smoke-related oxidative damage was demonstrated by a significant enhancement of 8-hydroxy-2'-deoxyguanosine in lung DNA, In parallel, there was a time-related induction of lung microsomal arylhydrocarbon hydroxylase activity, an elevation in cytosolic glutathione S-transferase activity, and a moderate but progressive and significant depletionof reduced glutathione, After discontinuing exposure to environmental cigarette smoke for 1 week, DNA adduct levels significantly dropped in the lung, tracheal epithelium, heart and bladder. The decrease was evident but not statistically significant in BAL cells, and was negligible in the heart. The selective localization and the differential persistence of these promutagenic nucleotide modifications in rat organs, tissues and cells suggest thatexposure to environmental cigarette smoke, at least under the high exposure regimens used in experimental studies, may pose a potential risk of developing mutation-related diseases.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 08/07/20 alle ore 06:19:08