Abstract LB-430: Chemopreventive effect of beta-cryptoxanthin on smoke-induced lung inflammation and lesions in ferrets

Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC Background: High intake of beta-cryptoxanthin has been associated with a decreased risk of lung cancer, particularly among current smokers in epidemiological studies. However, there are no available data from well-controlled animal studies to examine the effect of beta-cryptoxanthin on smoke-induced lung lesions and potential biological mechanisms by which beta-cryptoxanthin affects lung carcinogenesis. Using a ferret animal model, we evaluated the effect of beta-cryptoxanthin supplementation in both low-and high-dose (7.5 mcg/kg body weight per day vs. 37.5 mcg/kg body weight per day in ferrets which are equivalent to 104 mcg/day vs. 520 mcg/day, respectively, in the humans) on the cigarette smoke-induced pro-inflammatory cytokine TNF alpha, inflammation and squamous metaplasia in the lung. Methods: Thirty six male ferrets were assigned to one of six groups (n = 6 in each group) for 9 weeks as follows: 1) control; 2) cigarette smoke exposed; 3) low-dose beta-cryptoxanthin (7.5 mcg/kg body weight per day); 4) high-dose beta-cryptoxanthin (37.5 mcg/kg body weight per day); 5) cigarette smoke-exposed plus low-dose beta-cryptoxanthin; and 6) cigarette smoke-exposed plus high-dose beta-cryptoxanthin. Lung TNF alpha was measured by immunohistochemical staining. Lung inflammation and squamous metaplasia were quantified by histopathological evaluations. Results: Beta-cryptoxanthin supplementation dose-dependently increased plasma and lung beta-cryptoxanthin levels in ferrets. Cigarette smoke exposure lowered plasma and lung beta-cryptoxanthin levels. Treatment with beta-cryptoxanthin substantially reduced the cigarette smoke-elevated TNF alpha levels in bronchial/bronchiolar epithelial cells, alveolar epithelial cells, airway serous/mucous glands and lung macrophages. Beta-cryptoxanthin at both doses also significantly decreased the cigarette smoke-induced lung inflammation. In addition, both doses of beta-cryptoxanthin significantly lowered the incidence of lung squamous metaplasia induced by cigarette smoke exposure. There were no detectable squamous metaplasia in the groups treated with beta-cryptoxanthin alone and in the control group. Conclusions: Beta-cryptoxanthin may provide a beneficial effect against the smoke-induced lung inflammation and lung lesions. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-430.