Summary
Decreased superoxide dismutase (SOD) activity has been reported in various hyperproliferative keratinocytes. In order to elucidate the relationship between epidermal SOD activity and keratinocyte proliferation, we employed in vivo UVB irradiation. Following UVB irradiation at twice the minimum erythema dose, pig epidermis revealed an initial decrease in thymidine incorporation and mitotic counts for at least 48 h, followed by a marked increase, the peak of which was observed at 96 h after irradiation, and a return to basal levels by 5–7 days. The SOD activity remained constant during the initial 48 h and then decreased to about 50% at 96 h, mainly due to a decresed Cu,Zn-SOD activity. Our results indicate that the increased keratinocyte proliferation induced by UVB irradiation is accompanied by a decrease in SOD activity, and that this decrease is mainly due to a decreased Cu,Zn-SOD activity. No alteration in SOD activity was noted during the initial hypoproliferative phase following irradiation.
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References
Borek C, Troll W (1983) Modifiers of free radicals inhibit in vitro the oncogenic actions of X-rays, bleomycin, and the tumor promoter 12-O-tetradecanoylphorbol 13-acetate. Proc Natl Acad Sci USA 80:1304–1307
Carraro C, Pathak MA (1988) Characterization of superoxide dismutase from mammalian skin epidermis. J Invest Dermatol 90:31–36
Danno K, Horio T, Takigawa M, Imamura S (1984) Role of oxygen intermediates in UV-induced epidermal cell injury. J Invest Dermatol 83:166–168
Epstein JH (1978) Photocarcinogenesis: a review. Natl Cancer Inst Monograph 50:13–25
Epstein JH, Fukuyama K, Fye K (1970) Effects of ultraviolet radiation on the mitotic cycle and DNA, RNA and protein synthesis in mammalian epidermis in vivo. Photochem Photobiol 12:57–65
Fischer SM, Cameron GS, Baldwin JK, Jasheway DW, Patrick KE (1988) Reactive oxygen in the tumor promotion stage of skin carcinogenesis. Lipids 23:592–597
Fridovich I (1978) The biology of oxygen radicals. Science 201:875–880
Fridovich I (1983) Superoxide radical: an endogenous toxicant. Annu Rev Pharmacol Toxicol 23:239–257
Fuchs J, Huflejt ME, Rothfuss LM, Wilson DS, Carcamo G, Packer L (1989) Impairment of enzymic and nonenzymic antioxidants in skin by UVB irradiation. J Invest Dermatol 93:769–773
Hodgson EK, Fridovich I (1975) The interaction of bovine erythrocyte superoxide dismutase with hydrogen peroxide: inactivation of the enzyme. Biochemistry 14:5294–5299
Iizuka S, Taniguchi N, Makita A (1984) Enzyme-linked immunosorbent assay for human manganese-containing superoxide dismutase and its content in lung cancer. J Natl Cancer Inst 72:1043–1049
Iizuka H, Adachi R, Koizumi H, Aoyagi T, Ohkawara A, Miura Y (1984) Effect of adenosine and 2′-deoxyadenosine on epidermal keratinocyte proliferation: its relation to cyclic AMP formation. J Invest Dermatol 82:608–612
Iizuka H, Kajita S, Ohkawara A (1985) Ultraviolet radiation augments epidermal beta-adrenergic adenylate cyclase response. J Invest Dermatol 84:401–403
Ishiguro I, Shinohara R, Ishikura A, Naito J (1974) Formation of the red neotetrazolium formazan by reduced nicotinamide adenine dinucleotide phosphate-cytochrom c reductase in the presence of Triton X-100. Chem Pharm Bull (Tokyo) 22:2935–2940
Ishikawa M, Yaginuma Y, Hayashi H, Shimizu T, Endo Y, Taniguchi N (1990) Reactivity of a monoclonal antibody to manganese superoxide dismutase with human ovarian carcinoma. Cancer Res 50:2538–2542
Konstantinov AA, Peskin AV, Popova EY, Khomutov GB, Ruuge EK (1987) Superoxide generation by the respiratory chain of tumor mitochondria. Biochim Biophys Acta 894:1–10
Krieg L., Kuhlmann I, Marks F (1974) Effect of tumor-promoting phorbol esters and of acetic acid on mechanisms controlling DNA-synthesis and mitosis (chalones) and on the biosynthesis of histidine-rich protein in mouse epidermis. Cancer Res 34:3135–3146
Liotti FS, Menghini AR, Guerrieri P, Mariucci G, Locci P, Bruschelli G (1988) Possible role of certain antioxidant enzymes in dimethylnitrosamine-induced liver carcinogenesis. Int J Cancer 42:803–806
Lowe NJ (1981) Ultraviolet light and epidermal polyamines. J Invest Dermatol 77:147–153
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275
Marklund SL, Westman NG, Lundgren E, Roos G (1982) Copper- and zinc-containing superoxide dismutase, catalase, and glutathione peroxidase in normal and neoplastic human cell lines and normal human tissues. Cancer Res 42:1955–1961
Matsui MS, Laufer L, Scheide S, DeLeo V (1989) Ultraviolet-B (280–320 nm)-irradiation inhibits epidermal growth factor-binding to mammalian cells. J Invest Dermatol 92:612–622
Miyachi Y, Imamura S, Niwa Y (1987) Decreased skin superoxide dismutase activity by a single exposure of ultraviolet radiation is reduced by liposomal superoxide dismutase pretreatment. J Invest Dermatol 89:111–112
Nakamura Y, Gindhart TD, Winterstein D, Tomita I, Seed JL, Colburn NH (1988) Early superoxide dismutase-sensitive event promotes neoplastic transformation in mouse epidermal JB6 cells. Carcinogenesis 9:203–207
Oberley LW, Buettner GR (1979) Role of superoxide dismutase in cancer: a review. Cancer Res 39:1141–1149
Ogura R, Ueta H, Sugiyama M, Hidaka T (1990) Distribution of superoxide dismutase activity in the epidermis: measurement with electron spin resonance spin trapping. J Invest Dermatol 94:227–229
Ohkuma N, Matsuo S, Iizuka H, Ohkawara A (1987) Superoxide dismutase in epidermis. J Dermatol (Tokyo) 14:218–223
Ohkuma N, Kajita S, Iizuka H (1987) Superoxide dismutase in epidermis: its relation to keratinocyte proliferation. J Dermatol (Tokyo) 14:562–568
Pence BC, Naylor MF (1990) Effects of single-dose ultraviolet radiation on skin superoxide dismutase, catalase, and xanthine oxidase in hairless mice. J Invest Dermatol 95:213–216
Perchellet J-P, Abney NL, Thomas RM, Perchellet EM, Maatta EA (1987) Inhibition of multistage tumor promotion in mouse skin by diethyldithiocarbamate. Cancer Res 47:6302–6309
Rico MJ, Halprin KM, Baker L, Cayer M, Taylor JR (1985) Stimulated mitotic counts in the non-lesional skin of patients with psoriasis and controls. Br J Dermatol 113:185–188
Schallreuter KU, Wood JM (1989) Free radical reduction in the human epidermis. Free Radical Biol Med 6:519–532
Solanki V, Rana RS, Slaga TJ (1981) Diminution of mouse epidermal superoxide dismutase and catalase activites by tumor promoters. Carcinogenesis 2:1141–1146
Suzuki H, Fukuyama K, Epstein JH, Epstein WL (1978) Ultrastructural study of the nuclei in premitotic and repair DNA synthesis following UVB injury. J Invest Dermatol 71:334–339
Sykes JA, MacCormack FX Jr, O'Brien TJ (1978) A preliminary study of the superoxide dismutase content of some human tumors. Cancer Res 38:2759–2762
Taylor JR, Halprin KM, Levine V (1980) Inhibitors of epidermal cell DNA synthesis in surviving pig skin in vitro. J Invest Dermatol 74:125–130
Tisdale MJ, Mahmoud MB (1983) Activities of free radical metabolizing enzymes in tumours. Br J Cancer 47:809–812
Tyler DD (1975) Polarographic assay and intracellular distribution of superoxide dismutase in rat liver. Biochem J 147:493–504
Verma AK, Lowe NJ, Boutwell RK (1979) Induction of mouse epidermal ornithine decarboxylase activity and DNA synthesis by ultraviolet light. Cancer Res 39:1035–1040
Westman NG, Marklund SL (1981) Copper- and zinc-containing superoxide dismutase and manganese-containing superoxide dismutase in human tissues and human malignant tumors. Cancer Res 41:2962–2966
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Hashimoto, Y., Ohkuma, N. & Iizuka, H. Reduced superoxide dismutase activity in UVB-induced hyperproliferative pig epidermis. Arch Dermatol Res 283, 317–320 (1991). https://doi.org/10.1007/BF00376620
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DOI: https://doi.org/10.1007/BF00376620