Mechanisms of Tumor Promotion

TABLE 24.6. Some General Mechanisms of Tumor Promotion Selective Proliferation of Initiated Cells 

Increased responsiveness to and/or production of growth factors, hormones, and other active molecules 

Decreased responsiveness to inhibitory growth signals Perturbation of intracellular signaling pathways 

Inhibition of terminal differentiation of initiated cells Acceleration of differentiation of uninitiated cells 

Inhibition of apoptosis in initiated cells stimulation of the apoptosis of uninitiated cells 

---

Human data as well as studies in animals have provided negative evidence of carcinogenicity for endosulfan (Hack et al. 1995 Hoechst 1988b, 1989a). However, endosulfan promoted the development of altered hepatic foci in rats initiated with nitrosodiethylamine (Fransson-Steen et al. 1992). Although the mechanism of tumor promotion of endosulfan is not known, it has been suggested that it involves inhibition of cellular communication (Kenne et al. 1994). A brief discussion of this topic is provided in Section 2.5 under Cancer Effects. 

Slaga, T.J. "Mechanisms of Tumor Promotion, Vol. II" CRC Press Boca Raton, Florida, 1984. 

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). 

Fig. (17). Mechanism of tumor promotion with okadaic acid.

Although the molecular mechanisms of tumor-promoting action of... 

Slaga, T.J. Sivak, A. Boutwell, R.K. Eds. "Carcinogenesis - A Comprehensive Survey. Vol. 2. Mechanism of Tumor Promotion and Cocarcinogenesis" Raven Press New York, 1978. 

Tumor promoters alter pathways that cooperate with the genetic changes present in the initiated cell to produce the selective growth of that cell. Generic mechanisms of tumor promotion are shown in Table 24.6. Although the precise molecular/bio-chemical mechanisms of tumor promotion are unknown, we do know that certain receptors, growth factors, transcription factors, cytokines, and kinases are involved in tumor promotion induced by a particular tumor promoter. 

Slaga, T. J. (ed.). (1983). Tumor Promotion in Internal Organs, Volume 1 of Mechanisms of Tumor Promotion, CRC Press, Boca Raton, FL, pp. 1-179. 

Troll, W., and Wiesner, R. (1985). The role of oxygen radicals as a possible mechanism of tumor promotion. Annu Rev Pharmacol Toxicol 25, 509-528. 

A variefy of chemical agents are known to act as tumor promoters in various systems. However, much of our knowledge of the cellular and molecular mechanisms of tumor promotion has come from studies using the phorbol ester tumor promoters in the mouse skin model and in various cell culture systems. 

Van Duuren, B.L., G. Witz, and B.M. Goldschmitt Structure-activity relationships of tumor promoters and cocarcinogens and interaction of phorbol myristate acetate and related esters with plasma membranes in Mechanism of tumor promotion and carcinogenesis. Vol. II, edited by T.J. Slaga, A. Sivak, and R.K. Boutwell, Raven Press, New York, NY (1978) pp. 491-507. 

Wright SC, Zhong J, Larrick JW. Inhibition of apoptosis as a mechanism of tumor promotion. FASEB J 1994 8 654-660. 

Sivak, A., Mechanisms of Tumor Promotion and Cocarcinogenesis A Summary from One Point of View. In T.J. Slaga, A. Sivak, R.K. Boutwell, eds. "Carcinogenesis - A Comprehensive Survey - Volume 2", Raven Press, New York, N.Y., 1978, 553-564. Miller, E.C., Some Current Perspectives on Chemical Carcinogenesis in Humans and Experimental Animals Presidential Address, Cancer Research, 1978, 38 1479-1496. 

Reddy, B.S. Welsburger, J.H. Wynder, E.L. Mechanisms of Tumor Promotion and Cocarclnogenesls, Raven Press, New York 1978, 453-64. 

Pitot HC, Barsness L, Kitagawa T (1978) Stage in process of hepatocarcinogenesis in rat liver. In Slage TJ, Sivak A, Boutwell RK (eds) Mechanisms of tumor promotion and carcinogenesis. Raven Press, New York, p 433... 

---