Inhibitory effect of mandarin juice rich in beta-cryptoxanthin and hesperidin on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced pulmonary tumorigenesis in mice.
Previously we reported that a commercial Satsuma mandarin (Citrus unshiu Marc.) juice (MJ), MJ2 and MJ5, especially MJ5, effectively suppressed chemically-induced rat colon carcinogenesis (Int. J. Cancer 88 (2000) 146). MJ2 and MJ5 prepared from MJ have higher amounts of beta-cryptoxanthin and hesperidin than MJ, suggesting that principle chemopreventive factors in MJs may be beta-cryptoxanthin and hesperidin. Present study was conducted to test whether these MJs could modify carcinogenesis in other organ, lung initiated with 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in male A/J mice. Mice were given an intraperitoneal injection of NNK (10 micromol in saline/mouse) to induce pulmonary neoplasms. They also received MJ, MJ2 or MJ5 as a drinking water at night for 21 weeks, starting 1 week after the NNK injection. Treatments with MJ, MJ2, and MJ5 reduced the incidence of lung tumors and the inhibition by MJ5 (29% reduction) was statistically significant (P<0.05). MJs treatment lowered the multiplicity of lung neoplasms without statistical significance. Immunohistochemically, MJs, especially MJ5, reduced proliferating cell nuclear antigen (PCNA)-positive index in the lung tumors without affecting PCNA index in hyperplastic alveolar cell lesions. These findings might suggest that MJ5, which contain 3.9 mg beta-cryptoxanthin and 100 mg hesperidin in 100 g sample), has chemopreventive ability against NNK-induced mouse lung tumorigenesis.
Kohno
H
H
Department of Pathology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa 920-0293, Japan.
Taima
M
M
Sumida
T
T
Azuma
Y
Y
Ogawa
H
H
Tanaka
T
T
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D001628:Beverages; D002273:Carcinogens / Q000633:toxicity*; D002957:Citrus; D065366:Cryptoxanthins; D006569:Hesperidin / Q000494:pharmacology*; D007124:Immunoenzyme Techniques; D015994:Incidence; D007274:Injections, Intraperitoneal; D008175:Lung Neoplasms / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D009602:Nitrosamines / Q000633:toxicity*; D009697:Nucleolus Organizer Region / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D024341:Xanthophylls; D019207:beta Carotene / Q000031:analogs & derivatives* / Q000494:pharmacology*
D016588:Anticarcinogenic Agents; D002273:Carcinogens; D065366:Cryptoxanthins; D009602:Nitrosamines; D018809:Proliferating Cell Nuclear Antigen; D024341:Xanthophylls; D019207:beta Carotene; C016583:4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone; D006569:Hesperidin