Promotion stage

There are numerous reports of the effects of antioxidant vitamins on transformation. Vitamin C suppresses x-ray-induced transformation when CSHlOTy cells are treated daily for one week following irradiation (97), suppresses transformation by y-rays or neutrons, and prevents the promotion of radiation-induced transformation by 12-0-tetradecanoylphorbol 13-acetate (TPA), but has no effect on cell survival (98). In these studies, the continuous presence of vitamin C for a critical period appears to be necessary for suppression of transformation. Vitamin C may act on the promotion stage of... 

Antitumour activity has been reported for alkyltins, particularly dibutyltin. The effect in mouse skin initiation/promotion protocols showed dibutyltin inhibiting the promotion stage (Arakawa Wada,... 

VERGHESE M, RAO D R, CHAWAN C B, WILLIAMS L L, SHACKELFORD L (2002) Dietary inului suppresses azoxymethane-induced aberrant crypt foci and colon tumors at the promotion stage in young fisher 344 rats. J. Nutr. 132 2809-2813. 

Carcinogenesis develops in three stages initiation, promotion, and progression. Chem-ical substances can act at the initiation stage or at the promotion stage. Moreover, some chemicals have both initiating and promoting activities. 

As the involvement of free radicals in both the initiation and promotion stages of cancer has been demonstrated (see above), it is reasonable to suggest that antioxidants may be applied for cancer treatment and prevention. Therefore, already for a long time, the effects of many antioxidants and antioxidant enzymes on cancer development have been studied under in vitro and in vivo conditions. Naturally from the beginning, much attention has been drawn to the study of possible SOD effects. Unfortunately, natural SOD has a short circulation lifetime and unable to penetrate into cells. Therefore, various SOD mimics were studied as potential anticancer drugs. 

Now most people are not exposed to PAHs in this way, and no one is exposed to the phorbol esters, which are strictly laboratory chemicals. But this is not the point. The Berenblum-Shubik promotion studies, and hundreds more that have been explored in the past five decades, have contributed substantially to our understanding of the carcinogenic process. Some chemicals appear to possess both initiating and promoting properties - they are complete carcinogens - while others seem to be primarily involved in the promotion stage of the process. 

Serraino, M. and Thompson, L.U. 1992. The effect of flaxseed supplementation on the initiation and promotional stages of mammary tumorigenesis. Nutr. Cancer 17, 153-159. 

Black, H.S., Thornby, J.I., Gergius, J., and Lenger, W., Influence of dietary omega-6, -3 fatty acid sources on the initiation and promotion stages of photocarcinogenesis, Photochem. Photobiol., 56, 195, 1992. 

Continuous feeding of rats with 1% fenugreek seed powder (FSP) and 0.05% and 0.10% diosgenin suppressed total colonic aberrant crypt foci (ACF) by up to 32, 24 and 42%, respectively, in azoxymethane-induced carcinogenesis in rats. During the promotional stages, FSP inhibited total ACF. 

Murakoshi, M. et al.. Potent preventive action of a-carotene against carcinogenesis spontaneous liver carcinogenesis and promoting stage of lung and skin carcinogenesis in mice are suppressed more effectively by a-carotene than by P-carotene, Cancer Res., 52, 6583, 1992. 

Inano, H., Onoda, M., Inafuku, N., Kubota, M., Kamada, Y., Osawa, T., Kobayashi, H., and Wakabayashi, K., Chemoprevention by curcumin during the promotion stage of tumorigenesis of mammary gland in rats irradiated with gamma-rays. Carcinogenesis, 20, 1011, 1999. 

Can be compiete carcinogens Tumoligemcity is dose responsive No theoreticai threshold Nonmutagenic Threshold, reversible Tumorigenicity is dose responsive May function at tumor promotion stage No direct DNA damage Species, strain, tissue specificity... 

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