Skin Carcinogenesis

O Exposure to ultraviolet radiation from the sun is recognized as one of the primary triggers for skin carcinogenesis. Based on their wavelengths, UV radiation is divided into three components UVA (320 00 nm), UVB (280-320 nm), and UVC (200-280 nm).15 UVB accounts for only 5% of the solar radiation that reaches the earth, but it is the primary carcinogenic component in the UV spectrum.15 The following sequence of events describes the process in which UV radiation causes skin cancer (1) UV radiation reaches the earth, and on the skin, it reaches the cells in the epidermal layer (i.e., squamous cells, basal cells, and melanocytes),16 (2) the UV radiation (specifically... 

Ponnamperuma, R.M., Shimizu, Y., Kirchhof, S.M., and De Luca, L.M. 2000. Beta-carotene fails to act as a tumor promoter, induces RAR expression, and prevents carcinoma formation in a two-stage model of skin carcinogenesis in male Senear mice. Nutr Cancer 37 82-88. 

Wang ZY, Huang M, Lou Y, Xie J, Reuhl K, Newmark H, Ho C, Yang C and Conney A. 1994. Inhibitory effects of black tea, green tea, decaffeinated black tea, and decaffeinated green tea on ultraviolet B light-induced skin carcinogenesis in 7,12-dimethylbenz[<3]anthracene-initiated SKH-1 mice. Cancer Res 54(13) 3428-3435. 

Moore, R. et al., Tumor necrosis factor-[alpha], deficient mice are resistant to skin carcinogenesis, Nat Med., 5, 828, 1999. 

Mustacich, D. et al., Increased skin carcinogenesis in a keratinocyte directed thioredoxin-1 transgenic mouse, Carcinogenesis, 25, 1983, 2004. 

Thomas et al. (43) showed that phenanthrene is actively metabolized in salmonTds and Lee et al. (41) have shown that benzo[a]pyrene is biodegraded in three species of marine fish. Varanasi et al. (VI ) demonstrated for the first time that the skin of fish exposed to aromatic hydrocarbons via either force-feeding, intraperitoneal injection, or in flowing seawater accumulate substantial concentrations of metabolic products. This is of particular interest since studies of mammalian systems have shown that some alkyl naphthalenes can be accelerators of skin carcinogenesis (32). Varanasi et al. (11) also demonstrated that the mucus of rainFow trout exposed to radiolabeled naphthalene... 

Lee, J.-Y., Shin, J.-W., Chun, K.-S., Park, K.-K., Chung, W.-Y., Bang, Y.-J., Sung, J.-H., and Surh, Y.-J. (2005). Antitumor promotional effects of a novel intestinal bacterial metabolite (lH-901) derived from protopanaxadiol-type ginsenosides in mouse skin. Carcinogenesis 26, 359-367. 

Reiners JJ Jr et al Murine susceptibility to two-stage skin carcinogenesis is influenced by the agent used for promotion. Carcinogenesis 5 301-307, 1984... 

Fare G Rat skin carcinogenesis by topical applications of some azo dyes. Cancer Res 26 2405-2408, 1966... 

Toxicology. Indenol(l,2,3-ci)pyrene (IP) is a complete carcinogen and an initiator for skin carcinogenesis in the mouse. ... 

The same study demonstrated that 10 paintings at 2-day intervals for a total dose of 250pg IP initiated skin carcinogenesis, hr 30 mice subsequently treated with croton oil in acetone, a total of 10 papillomas in 5 animals was produced. 

Yuspa SH (1998) The pathogenesis of squamous cell cancen lessions learned from studies of skin carcinogenesis. J Dermatol Sd 17 1-7... 

Kurokawa Y, Takamura N, Matsushima Y, et al. 1984. Studies on the promoting and complete carcinogenic activities of some oxidizing chemicals in skin carcinogenesis. Cancer Lett 24 299-304. 

S. M. Fischer, H.-H. Lo, G.B. Gordon, K. Seibert, G. Kelloff, R.A. Lubet, C.J. Conti, Chemopreventive activity of celecoxib, a specific cyclooxygenase-2 inhibitor, and indomethacin against ultraviolet light-induced skin carcinogenesis. Mol. Carcinog. 25 (1999) 231. 

CN210 Berton, T. R., S. M. Fischer, C. J. Conti, and M. F. Locniskar. Comparison of ultraviolet light-induced skin carcinogenesis and ornithine decarboxylase activity in sencar and hairless SKH-1 mice fed a constant level of dietary lipid varying in com and coco-... 

Gwynn and Salaman H tested a number of compounds, Including CN, as possible promoters of skin carcinogenesis when 9,10-dimethyl-1,2-benzanthracene (DMBA) was used as an initiator. Treatment consisted of 0.3 ml of a 0.1% or 0.15% acetone solution of DMBA on the clipped backs of mice, followed after a delay of 21 d by application of CN at a maximal tolerated concentration once or twice a week for 12-15 wk. There was a significant increase in tumors 22 wk after the start of secondary treatment. 

Deila Porta, G., Rappaport, H. and Saffiotti, U. (1956). Induction of melanotic lesions during skin carcinogenesis in hamsters, AMA Archives of Pathology 61,305. 

Murakoshi, M., Nishino, H., Tokuda, H., Iwashima, A., Okuzumi, J., Kitano, H., and Iwasaki, R. (1992). Inhibition by squalene of the tumor promoting activity of 12 o-tetradecanoylphorbol-13 acetate in mouse skin carcinogenesis. Int. ]. Cancer 52,950-952. 

Some information on structure-promotion relationships for PBBs is available from studies that used two-stage liver and skin carcinogenesis models. In the liver promotion studies, development of enzyme-altered hepatic foci (putative preneoplastic lesions) was assessed in rats that were partially hepatectomized, initiated with diethylnitrosamine and promoted with PBBs (Buchmann et al. 1991 Dixon et al. 1988 ... 

Patamalai, B., Burow, D.L., Gimenez-Conti, I., Zenklusen. J.C.. Conti, C.J.. Klein-Szanto, A.J. Fischer, S.M. (1994) Altered expression of transforming growth factor-pi inRNAand protein in mouse skin carcinogenesis. Mol. Carcinog., 9, 220-229... 

In skin painting studies in mice, hydroquinone was inactive as an initiator of skin carcinogenesis. In bladder implantation studies, hydroquinone in cholesterol pellets increased the incidence of bladder carcinomas in mice (lARC, 1977). 

Phenol was tested for carcinogenicity by oral administration in rats in one study and in mice in one study. An increased incidence of leukaemia was reported in male rats treated with the lower dose but not in high-dose rats or in mice or female rats. Phenol was a promoter of mouse skin carcinogenesis in two-stage protocols. 

Spalding, J.W., Momma, J., Elwell, M.R. Tennant, R.W. (1993) Chemically induced skin carcinogenesis in a transgenic mouse line (TG-AC) carrying a v-Ha-ras gene. Carcinogenesis, 14, 1335-1341... 

Haesen, S., Timmermans, M. Kirsch-Volders, M. (1993) Induction of micronuclei and karyotype aberrations during in vivo mouse skin carcinogenesis. Carcinogenesis, 14, 2319-2327... 

Saffiotti U, Shubik P. 1963. Studies on promoting action in skin carcinogenesis. National Cancer Institute Monograph 10 489-506. 

DiGiovanni J, Viaje A, Berry DL, et al. 1977. Tumor-initiating ability of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and Arochlor 1254 in the two-stage system of mouse skin carcinogenesis. Bull Environ Contam Toxicol 18 552-556. 

Hennings, H., Blumberg, P. M., Pettit, G. R., Herald, C. L., Shores, R., and Yuspa, S. H., Bryostatin 1, an activator of protein kinase C, inhibits tumor promotion by phorbol esters in SENCAR mouse skin, Carcinogenesis, 8, 1343, 1987. 

In five of six nondietary tumor-promotion experiments, sodium selenide significantly reduced the number of mice with tumors induced by 7,12-dimethyl-benzanthracene (DMBA)-croton oil (1). In these experiments, sodium selenide was applied concomitantly along with croton oil to female Swiss albino mice initiated with DMBA. Riley has also observed a reduction in DMBA-phorbol ester carcinogenesis by sodium selenide (2). The effect of selenium-deficient and selenium-adequate diets on DMBA-croton oil and benzopyrene skin carcinogenesis has also been studied. Supplemental dietary selenium inhibited both types of carcinogenesis. 

Diwan BA, Ward JM, Rice JM, et al. 1985. Tumor-promoting effects of di(2-ethylhexyl)phthalate in JB6 mouse epidermal cells and mouse skin Carcinogenesis 6 343-397. 

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