Poster Topical Area: Carotenoids and Retinoids
Poster Board Number: 14
Background: Lung cancer and chronic obstructive pulmonary disease (COPD) are caused by cigarette smoke (CS). 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is the most potent carcinogen in CS. Epidemiological studies suggest inverse association between consumption of lycopene, a major carotenoid naturally occurring in tomatoes and tomato products, and risk of lung cancer.
Objectives: We hypothesize that lycopene protects against CS/NNK-induced COPD and preneoplastic lesions in lung of ferret.
Methods: Ferrets, a non-rodent model that mimics closely human carotenoid accumulation and lung lesions, were randomly divided into four groups (n=12-16/group): control, NNK+CS, NNK+CS+low lycopene (LL, 2.2 mg/kg BW/d) and NNK+CS+high lycopene (HL, 6.6 mg/kg BW/d). Ferrets in NNK+CS groups were given NNK (50 mg/kg BW, i.p. injection) once a month for four consecutive months, and were exposed to CS for 15 minutes/d over a 22-week period. Ferrets in lycopene feeding groups were fed with lycopene three weeks prior to NNK injection at two doses, LL and HL, which are equivalent to ~30 mg and ~90 mg of lycopene/d in human, respectively, and continued feeding over a 22-week period. Lycopene concentrations were measured by HPLC. Bronchitis was evaluated by histopathology defined by peribronchial/peribronchiolar/alveolar infiltrates of inflammatory cells. The degree of emphysema, the alveolar destruction, was assessed by the measurement of the mean linear intercept (Lm). Preneoplastic lesions, including squamous metaplasia and atypical adenomatous hyperplasia, were evaluated by histopathology.
Results: We did not observe a significant difference in body weights among groups. There was higher accumulation of lycopene in the HL group compared to the LL group in both plasma and liver. Both lycopene doses significantly inhibited CS/NNK-induced emphysema development, as compared with the NNK+CS alone (P < 0.05). HL feeding significantly inhibited bronchitis in the CS/NNK exposed group (P < 0.05), while LL feeding showed marginal significance (P = 0.09). Additionally, HL feeding significantly decreased CS/NNK-induced preneoplastic lesions development (P < 0.05).
Conclusions: These data provide strong supportive evidence of lycopene beneficial effect against COPD and pulmonary preneoplastic lesions.
Supported by NIH/NCI (CA176256) and USDA/ARS (58-1950-0074S)
Jelena Mustra Rakic