The effects of combined antioxidant (β‐carotene, α‐tocopherol and ascorbic acid) supplementation on antioxidant capacity, DNA single‐strand breaks and levels of insulin‐like growth factor‐1/IGF‐binding protein 3 in the ferret model of lung cancer

Abstract

Insulin‐like growth factor 1 (IGF‐1) and its major binding protein, IGF binding protein 3 (IGFBP‐3) are implicated in lung cancer and other malignancies. We have previously shown that the combination of three major antioxidants [β‐carotene (BC), α‐tocopherol (AT) and ascorbic acid (AA)] can prevent lung carcinogenesis in a 4‐(methylnitrosamino)‐1‐(3‐pyridyl)‐1‐butanone (NNK)‐treated and smoke‐exposed (SM) ferret model, which is highly analogous to humans. The present study is aimed at determining the effect of the combination of BC, AT and AA on antioxidant capacity, lymphocyte DNA damage, plasma IGF‐1 and IGFBP‐3 concentrations, as well as on IGF‐1/IGFBP‐3 mRNA expression in the tissues (lung and liver) of the ferrets. Ferrets were treated with or without combined antioxidant (BC, AT and AA) supplementation (AOX) for 6 months in the following 4 groups: (i) control; (ii) SM+NNK; (iii) AOX; and (iv) SM+NNK+AOX. Combined AOX supplementation significantly attenuated SM+NNK induced lymphocyte DNA damage in the ferret, while increasing resistance to oxidative damage when challenged with H2O2 in vitro. Ferrets treated with SM+NNK had significantly lower IGFBP‐3 mRNA expression in lungs, whereas there was significantly higher IGFBP‐3 mRNA expression in the liver, as well as higher circulating IGFBP‐3 concentrations. Combined AOX supplementation did not affect the plasma or tissue (lung and liver) ratio of IGF‐1/IGFBP‐3. Combined antioxidant supplementation provides protection against smoke‐induced oxidative DNA damage, but does not affect the IGF‐1/IGFBP‐3 system. Differential expression of IGFBP‐3 in different tissues indicates that caution should be taken when using plasma IGFBP‐3 as a biomarker of tissue status. © 2007 Wiley‐Liss, Inc.

Antiproliferation Properties of Grain Sorghum Dry Distiller’s Grain Lipids in Caco-2 Cells

“…As potent antioxidants, carotenoids can deactivate free radicals that damage the basic structure of cells and thus lead to cancer (40). However, carotenoids were not detected in the GS-DDG lipid sample under the conditions of the test and thus could not account for the cited antiproliferation results.…”

Development of ferret as a human lung cancer model by injecting 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK)

“…2). Since we have previously shown that NNK and cigarette smoke treatment resulted in increased ERK activation [37] and proliferating cellular nuclear antigen [31, 38-40], this could be due to the limited sample size or NNK treatment alone (without smoke exposure) in the present study. It has been reported that the expression of α7 nAChR was related to the major activation of the Rb-Raf-1/phospho-ERK pathway and was associated with proliferation of lung cancer cells [34, 41].…”

Short-term Betacarotene Supplementation Positively Affects Ovarian Follicular Development and Ovulation Rate in Goats

“…According to Cassano et al (19991, oxidative damage to the oocyte or Table 1 Least square means for body weight (BW), body condition score (BCS), total follicles (FT), total corpus luteum (CLT) and total ovarian activity (TOA=FT+CLT) in goats supplemented with betacorotene (BETA, 50 mg goat-' day-l) and no supplemented goats (CONTROL) In fact, betacarotene acts against lipid peroxidation as a n antioxidant molecule protecting several reproductive structures from oxidative DNA-damage (Kim et al, 2007). Betacarotene seems to act as a n ovarian-protective molecule, not only as luteoprotective (Haliloglu et al, 2002) but also improving embryo production a n d quality in superovulated cows (Sales et al, 2007), optimizing reproductive performance in females.…”