Promotion, in carcinogenesis

Exposure to ROS and RNS causes posttranslational modifications in p53 that inhibit cellular growth. Increase in iNOS expression causes mutations in p53 at codons 247 and 248. These have been observed in inflamed lesions of patients that have ulcerative colitis, associated with colon cancer. In colon tumors, there is a high correlation between iNOS activity and G C to A T mutations at methylcytosine sites in p53. Similarly, increased iNOS expression was associated with mutations in p53 in stomach, brain, and breast cancers. NO and its derivatives, which cause mutations in cancer-related genes such as p53 therefore act as endogenous initiators and promoters in carcinogenesis. 

Reddy, B.S., Weisburger, J.H. and Wynder,E.L., 1978, Colon cancer bile salts as tumor promoters. In "Carcinogenesis, Vol. 2, Mechanisms of Tumor Promotion and"Cocarcinogenesis," T.J. Slaga, A.Sivak and R.K. Boutwell, eds.. Raven Press, New York. 

Promotion refers to a set of cellular processes by which the normal balance between orderly cell replication and orderly cell death is tilted in favor of cell replication, ultimately resulting in the unrestrained replication of a cell line to form a tumor. The pivotal role of promotion in carcinogenesis shows that cancer is first and foremost a disease of the regulation of cell growth. Some examples of chemicals that promote carcinogenesis are shown in Figure 7.8. 

A scientifically evaluated and fully referenced data bank, developed and maintained by the National Cancer Institute (NCI). It contains some 8,000 chemical records with carcinogenicity, mutagenicity, tumor promotion, and tumor inhibition test results. Data are derived from studies cited in primaiy journals, current awareness tools, NCI reports, and other special sources. Test results have been reviewed by experts in carcinogenesis and mutagenesis. 

Nelson R.L. Chlorophyllin, an antimutagen, acts as a tumor promoter in the rat dimethylhydrazine colon carcinogenesis model. Anticancer Res., 12, 737, 1992. 

Zimmerman, R and Cerutti, P. (1984). Active oxygen acts as a promoter of carcinogenesis in C3H/10T1/2/C18 fibroblasts. Proc. Natl Acad. Sci. USA 81, 2085-2087. 

The interaction of carotenoids with cigarette smoke has become a subject of interest since the results of the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study Group 1994 (ATBC) and CARET (Omenn et al. 1996) studies were released. P-Carotene has been hypothesized to promote lung carcinogenesis by acting as a prooxidant in the smoke-exposed lung. Thus, the autoxidation of P-carotene in the presence of cigarette smoke was studied in model systems (toluene) (Baker et al. 1999). The major product was identified as 4-nitro-P-carotene, but apocarotenals and P-carotene epoxides were also encountered. 

Kitchin KT, Brown JL. 1989. Biochemical studies of promoters of carcinogenesis in rat liver. Teratog Carcinog Mutagen 9(5) 273-285. 

Gelderblom, W.C. et al.. Cancer promoting potential of different strains of Fusarium moniliforme in a short-term cancer initiation/promotion assay. Carcinogenesis, 9, 1405, 1988. 

As pointed out by Dixon and colleagues if a direct role for refluxed bile derivatives in carcinogenesis becomes accepted, therapy aimed principally at acid reduction, cannot be expected to eliminate cancer risk in Barrett s oesophagus. However, not only is acid suppression likely to be ineffective in preventing bile acid-driven carcinogenesis, it could also actually promote cancer development by providing a less acidic environment favouring bile acid activity. 

Moller L, Torndal UB, Eriksson LC, et al. 1989. The air pollutant 2-nitrofuran as initiator and promoter in a liver model for chemical carcinogenesis. Carcinogenesis 10(3) 435-440. 

T. Tamuara, and M. Takido. Inhibitory effect of cycloartenol ferulate, a OS090 component of rice bran, on tumor promotion in two-stage carcinogenesis in mouse skin. Biol Pharm Bull 1998 ... 

Boutwbll, R.K (1978). Biochemical mechanism of tumor promotion. page 49 in Carcinogenesis, VoL 2., Mechanisms of Tlimor Promotion and Carcinogenesis, Slaga, T.J., SiVAK, A. AND BouTWELL, R.K., Eds. (Raven Press, New York). 

Kennedy, A.R. (1984). Promotion and other interactions between agents in the induction of transformation in vitro in fibroblast-like cell culture systems, in Mechanisms of Thmor Promotion, VoL 3. Thmor Promotion and Carcinogenesis In Vitro, Slaga, T.J., Ed. (CRC Press, Inc., Cleveland, Ohio). 

As described in Chapter III, morusin (3) has been found to be anti-tumor promoter in a two-stage carcinogenesis experiment with teleocidin. Considering the similarity of the structures between morusin (3) and artonin E (7), artonin E (7) was expected to be an anti-tumor promoter. Furthermore we found a novel photo-oxidative cyclization of artonin E (7) as follow photo-reaction of artonin E (7) in CHCI3 containing 4% ethanol solution with high-pressure mercury lamp produced artobiloxanthone (8) and cycloartobiloxanthone (9), and the treatment of artonin E (7) with radical reagent (2,2-diphenyl-1-picrylhydrazyl DPPH) resulted in the same products, Fig. (15), [84]. 

Jensen RK, Sleight SD, Goodman JI, et al. 1982. Polybrominated biphenyls as promoters in experimental hepatocarcinogenesis in rats. Carcinogenesis 3 1183-1186. 

Ftirstenberger, G., Schurich. B., Kaina, B., Petrusevska, R.T., Fusenig, N.E. Marks, F. (1989) Tumor induction in initiated mouse skin by phorbol esters and methyl methanesulfonate correlation between chromosomal damage and conversion ( stage I of tumor promotion ) in vivo. Carcinogenesis, 10, 749-752... 

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