Abstract
Specific biochemical and genetic events that appear to be essential to promotion of transformation in JB6 cells have been identified.1 The two earliest events appear to be the activation of protein kinase C (PKC) (and the subsequent phosphorylation of its substrates) and an increase in oxidant stress. There is a significant body of evidence that implicates reactive oxygen, and the superoxide radical anion in particular, as an important mediator of tumor promotion.2 This evidence includes studies with nonphorbol tumor promoters as well as TPA, several tissues in vivo, and a number of different model systems in vitro. For example, copper(II)(3,5-diisopropylsalicylate)2 (CuDIPS) is a potent inhibitor of phorbol ester-mediated tumor promotion in the epidermis of CD-I mice.3 CuDIPS is a lipophilic copper complex that catalyzes the dismutation of the superoxide anion radical at a rate similar to that of SOD, its biological counterpart In vivo.4 In in vitro studies with JB6 P+ cells, SOD was observed to inhibit promotion of transformation by TPA. Other in vitro studies have demonstrated that SOD will inhibit TPA-dependent radiogenic transformation of C3H10T1/2 cells.5,6
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
N. H. Colburn, Genes and membrane signals involved in neoplastic transformation. In Huberman, E. (Ed.): The Role of Chemicals and Radiation in the Etiology of Cancer, 1985 (E. Huberman, Ed.) pp. 235–248. Raven Press, New York.
T. W. Kensler, Oxygen free radicals in chemical carcinogenesis. In Superoxide Dismutase, Vol. 3, 1986 (L. W. Oberley, Ed.) pp. 191–236. CRC Press, Boca Raton.
T. Kensler, D. M. Bush, and W. J. Kozumbo, Inhibition of tumor promotion by a biomimetic superoxide dismutase. Science 221, 75–77 (1983).
E. Lengfelder and U. Weser, Superoxide dismutation by low molecular weight copper complexes. Bull. Eur. Physiopathol. Resp. 17S, 73–90 (1981).
C. Borek and W. Troll, Modifiers of free radicals inhibit in vitro the oncogenic actions of x-rays, bleomycin, and the tumor promoter 12-0-tetradecanoylphorbol-13-acetate. Proc. Natl. Acad. Sci. USA 80, 1304–1307 (1983).
J. B. Little, A. R. Kennedy, and H. Nagasawa, Involvement of free-radical intermediates in oncogenic transformation and tumor promotion in vitro. In Radioprotectors and Anticarcinogens, 1983 (O. F. Nygaard and M. G. Simic, Eds.) pp. 487–502, Academic Press, Orlando.
J. Freidman and P. Cerutti, The induction of ornithine decarboxylase by phorbol 12-myristate-13-acetate or by serum is inhibited by antioxidants. Carcinogenesis 4, 1425–1427 (1983).
R. Zimnerman and P. Cerutti, Active oxygen acts as a promoter of transformation in mouse embryo C3H/10T1/2/C18 fibroblasts. Proc. Natl. Acad. Sci. USA 81, 2085–2087 (1984).
M. I. Lerman, G. A. Hegamyer, and N. H. Colburn, Cloning and characterization of putative genes that specify sensitivity to neoplastic transformation by tumor promoters. Int. J. Cancer 37, 293–302 (1986).
Y. Nakamura, N. H. Colburn, and T. D. Gindhart, Role of reactive oxygen in tumor promotion: Implication of superoxide anion in promotion of neoplastic transformation in JB6 cells by TPA. Carcinogenesis 6, 229–235 (1985).
Y. Nakamura, T. D. Gindhart, D. Winterstein, J. L. Seed, I. Tomita, and N. H. Colburn, Early superoxide dismutase sensitive event promotes neoplastic transformation in mouse epidermal JB6 cells. Carcinogenesis, in press (1987).
T. Imanari, M. Hirota, M. Miyazaki, K. Hayakawa, and Z. Tamura, Improved assay procedure for the determination of superoxide dismutase activity. Igaki no Ayumi 101, 497–497 (1977).
V. Solanki, R. S. Rana, and T. J. Slaga, Diminution of mouse epidermal superoxide dismutase and catalase activities by tumor promoters. Carcinogenesis 2, 1141–1146 (1981).
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1987 Plenum Press, New York
About this chapter
Cite this chapter
Seed, J.L., Nakamura, Y., Colbourne, N.H. (1987). Implication of Superoxide Radical Anion in Promotion of Neoplastic Transformation in Mouse JB6 Cells by TPA. In: Cerutti, P.A., Nygaard, O.F., Simic, M.G. (eds) Anticarcinogenesis and Radiation Protection. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-6462-1_28
Download citation
DOI: https://doi.org/10.1007/978-1-4615-6462-1_28
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4615-6464-5
Online ISBN: 978-1-4615-6462-1
eBook Packages: Springer Book Archive