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.