The direct influence of P-cryptoxanthin intake on the development of colon tumors has been studied in F344 rats (Narisawa et al., 1999 ). N-methyl-nitrosourea-induced colon cancer in rats is significantly reduced for those given high doses of P-cryptoxanthin (25 ppm dietary level). Twenty-four (96%) of 25 control rats compared to only 17 (68%) of 25 P-cryptoxanthin-supplemented rats developed tumors during the 30-week study (p < 0.02). Lower doses of 1 or 5 ppm did not produce a statistically significant reduction in the number of tumors observed in similar study groups. Tissue levels were significantly elevated for the high-dose animals but not for those given the lower doses. Another rodent study (Nishino et al., 1999) investigated the effect of P-cryptoxanthin against tumorigenesis in mouse skin. Skin cancer was induced in 15 SENCAR mice, which were consuming P-cryptoxanthin at a level of 25 ppm in drinking water, by treatment with peroxynitrite and promotion with TPA (12-O-tetradecanoylphorbol-13-acetate). Comparison to 15 control mice revealed a modest, statistically significant reduction in the number of tumors among the P-cryptoxanthin-supplemented animals. A similar experiment with ICR mice in which skin cancer was induced with dimethyl benz[a]anthracene [DMBA] showed that P-cryptoxanthin administration resulted in a 29% tumor rate compared to a 64% rate in the mice not supplemented with the carotenoid. The authors concluded that P-cryptoxanthin is effective at inhibiting tumor formation and that it functions by stimulating the expression of the RB oncogene (Nishino et al., 2000).
Effective gap-junctional communication is an important functional characteristic in healthy multicellular tissues (Stahl et al., 1997; Stahl et al., 1998; Zhang et al., 1991). Gap junctions are direct channels connecting adjacent cells, which permit transfer between cells of molecules having masses below about 1000 amu, and are formed by a class of proteins referred to as connexin proteins. Gap-junctional communication is important in exchange of nutrients, ions, and signaling compounds.
There is a developing understanding that gap-junctional communication, or the lack thereof is important to the mechanisms of carcinogenesis and teratogenesis. A number of carotenoids are effective at stimulating gap-junctional communication, including P-cryptoxanthin. Importantly, the ability of carotenoids to induce gap-junctional communication is apparently unrelated to their antioxidant abilities.
It is apparent that there remains a considerable void in our knowledge of the influence of P-cryptoxanthin on human health and disease processes. Despite this, a fairly significant body of evidence supports the hypothesis that P-cryptoxanthin is effective as an antioxidant, and that it may play a role either directly or indirectly in the stimulation of important cell regulatory functions including cell gap-junctional communication and possibly oncogene stimulation.
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