title: Effects of 6-month daily supplementation with oral beta-carotene in combination or not with benzo[a]pyrene on cell-cycle markers in the lung of ferrets.
abstract: Epidemiological studies have demonstrated that people who eat more fruits and vegetables (rich in carotenoids) and people who have higher serum beta-carotene (BC) levels have a lower risk of cancer, particularly lung cancer. However, the two main human intervention studies of BC supplementation (the ATBC and the CARET trials) revealed an increased risk of lung cancer among smokers and asbestos workers. Previous studies carried out in the ferret have reported that BC effects are related to dose. Here, we treated ferrets with two concentrations of oral BC (0.8 and 3.2 mg/kg body weight per day) for 6 months, using BC in a formulation also containing dl-alpha-tocopherol and ascorbyl palmitate. The effect of the smoke-derived carcinogenic agent benzo[a]pyrene (BP), with or without low-dose BC, was also analysed. We determined the protein levels and mRNA expression levels of activator protein 1 (c-Jun and c-Fos), c-Myc, cyclin D1, proliferating cellular nuclear antigen and retinoic acid receptor beta. We did not find higher levels of cell proliferation markers in the lung of ferrets treated with BC or signals of squamous metaplasia lesions either. On the other hand, although no evident signals of pulmonary carcinogenesis were observed in animals exposed to BP, BC supplementation in these animals may prevent against excess cell proliferation, since this reestablishes Jun protein and cyclin D1 mRNA levels in the lung of BP-exposed animals. In summary, these results show that the combination of BC with alpha-tocopherol and ascorbyl palmitate does not induce pro-oxidant effects in the lung of ferrets.
authors.affiliation: Departament de Biologia Fonamental i Ciències de la Salut, Universitat de les Illes Balears, Palma de Mallorca and CIBER Fisiopatología obesidad y nutrición (CB06/03) Instituto Salud Carlos III, Spain.
authors.forename: Antonia
authors.initials: A
authors.lastname: Fuster
authors.forename: Catalina
authors.initials: C
authors.lastname: Picó
authors.forename: Juana
authors.initials: J
authors.lastname: Sánchez
authors.forename: Paula
authors.initials: P
authors.lastname: Oliver
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Zingaretti
authors.forename: Incoronata
authors.initials: I
authors.lastname: Murano
authors.forename: Manrico
authors.initials: M
authors.lastname: Morroni
authors.forename: Ulrich
authors.initials: U
authors.lastname: Hoeller
authors.forename: Regina
authors.initials: R
authors.lastname: Goralczyk
authors.forename: Saverio
authors.initials: S
authors.lastname: Cinti
authors.forename: Andreu
authors.initials: A
authors.lastname: Palou
mesh_terms: D000818:Animals; D001205:Ascorbic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D001564:Benzo(a)pyrene / Q000633:toxicity*; D015415:Biomarkers / Q000032:analysis; D002453:Cell Cycle / Q000187:drug effects*; D019587:Dietary Supplements; D005260:Female; D005289:Ferrets / Q000502:physiology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009153:Mutagens / Q000633:toxicity*; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D011897:Random Allocation; D013997:Time Factors; D024502:alpha-Tocopherol / Q000008:administration & dosage / Q000494:pharmacology; D019207:beta Carotene / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D015415:Biomarkers; D009153:Mutagens; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D019207:beta Carotene; D001564:Benzo(a)pyrene; D024502:alpha-Tocopherol; D001205:Ascorbic Acid; C031226:6-O-palmitoylascorbic acid