Efeito de promotores tumorais em pele de gerbil, Meriones unguiculatus
DOI:
https://doi.org/10.32635/2176-9745.RBC.1995v41n3.2945Palabras clave:
Carcinogênese, Iniciação, Promoção, Pele, GerbilResumen
Supondo que a resistência relativa da pele de gerbil adulto à carcinogênese química estaria relacionada a um fenômeno de adaptação ao processo de promoção tumoral, foi caracterizado o efeito de óleo de cróton (OC) e peróxido de benzoíla (PB) sobre a pele de gerbil, através do estudo das alterações morfológicas, correlatas à atividade promotora e induzidas em função da dose administrada, da freqüência do tratamento e da associação ao iniciador metilcolantreno (MC) em modelos bifásicos e trifásicos de carcinogênese. Verificou-se que uma única aplicação tópica de 00 (0,94 mg e 1,88 mg) ou PB (20 mg e 40 mg) induz, na epiderme interfolicular, grau similar de hiperceratose e hiperplasia dose-dependente; outros efeitos, como espessamento da epiderme, hipertrofia celular e inflamação, eram mais acentuados pelo tratamento com OC. O efeito hiperplásico, também mais acentuado com OC, decorreria do estímulo proliferativo e do desequilíbrio entre proliferação e diferenciação epidérmica. O tratamento tópico repetido, com OC (1,41 mg) ou PB (30 mg), independente da freqüência semanal, bi-semanal ou tri-semanal, determinou diminuição do estímulo proliferativo inicial, além de intensa hiperceratose e regressão da hiperplasia, no caso do OC conseqüente ao desequilíbrio entre proliferação e diferenciação, favorecendo a perda celular. Entretanto, o PB, quando aplicado 2 ou 3 vezes/semana, determinou discreta progressão da hiperplasia inicial, decorrente de ligeiro desequilíbrio entre proliferação e diferenciação, prevalecendo discreto ganho celular. Ambas substâncias diferiram também no efeito inflamatório, ocorrendo regressão com OC e progressão com PB. A divergência nos efeitos hiperplásico e inflamatório estaria refletindo mecanismos de ação distintos destas duas substâncias. Ao ser aplicado OC ou PB após MC (0,2 mg), segundo protocolos de carcinogênese bifásica ou trifásica, comprovou-se que apenas o PB tem discreto efeito promotor - propagador – de papilomas na pele de gerbil adulto. Considerando a diminuição do estímulo proliferativo, que ocorre durante o tratamento repetido com OC e PB, associada ao efeito destas substâncias sobre a diferenciação celular - hiperceratose - entende-se que a expansão clonal seletiva de células epidérmicas estaria prejudicada, principalmente com OC, sendo talvez esta a base biológica da resistência relativa da pele de gerbil adulto à indução química de tumores de linhagem epidérmica.
Descargas
Citas
BOUTWELL, R.K. - Some biological aspects of skin carcinogenesis. Prog Exp Tumor Res, 4:207-250, 1964. DOI: https://doi.org/10.1159/000385978
BOUTvVELL, R.K.; VERMA, A.K.; ASHENDEL, CL.; ASTRUP, E. - Mouse skin: a useful model system for studying the mechanism of chemical carcinogenesis. Carcinog Compr Surti, 7.1 -12, 1982.
YUSPA, S.H. - Molecular and cellular basis for tumor promotion in mouse skin. Int Symp Princess Takamatsu Cancer Res Fund, 14.315-326, 1983.
GUZMÁN-SILVA, M.A.; GUIMARÃES, J.S.P. - Carcinogênese química cutânea. Rev Bras Cancerol, 31285-291, 1985.
BALMAIN, A.; BROWN, K.; AKHURST, R.J.; FEE, FM. - Molecular analysis of chemical carcinogenesis in the skin. Br J Cancer, 58(SuppLIX):72-75, 1988.
FÜRSTENBERGER, G.; BERRY, D.L.; SORG, B.; MARKS, F. - Skin tumor promotion by phorbol esters is a two-stage process. Proc Nati Acad Sci USA, 78.7722-7726, 1981. DOI: https://doi.org/10.1073/pnas.78.12.7722
SLAGA, T.J.; FISCHER, S.M.; WEEKS, C.E.; KLEIN-SZANTO, A.J.P.; REINERS, J. - Studies on the mechanisms involved in multistage carcinogenesis in mouse skin. J Ceil Biochem, 18.99-119, 1982. DOI: https://doi.org/10.1002/jcb.1982.240180109
HENNINGS, H.; YUSPA, S.H. - Two-stage tumor promotion in mouse skin: an alternative interpretation. JNCI, 74:735-740, 1985.
MARKS, F.; FÜRSTENBERGER, G. – Experimental evidence that skin carcinogenesis is a multistep phenomenon. Br J Dermatol, 115:1-8, 1986. DOI: https://doi.org/10.1111/j.1365-2133.1986.tb02100.x
MARKS, F.; FURSTENBERGER, G. - Multistage tumor promotion in skin. Int Symp Princess Takamatsu Cancer Res Fund, 14:273-287, 1983.
SLAGA, T.J.; FISCHER, S.M.; WEEKS, C.E.; KLEIN-SZANTO, A.J.P. - Multistage chemical carcinogenesis in mouse skin. Curr Probi Dermatol, 10:193-218, 1980. DOI: https://doi.org/10.1159/000396290
SLAGA, TJ.; BUTLER, A.P. - Cellular and biochemical changes during multistage skin tumor promotion. Int Symp Princess Takamatsu Cancer Res Fund, 14291- 301, 1983.
CHU, K.C.; BROWN, C.C.; TARONE, R.E.; TAN, W.Y. - Differentiating among proposed mechanisms for tumor promotion in mouse skin with the use of the multievent model for cancer. JNCI, 79:789-796, 1987.
HENNINGS, H.; BOWDEN, G.T.; BOUTWELL, R.K. - The effect of croton oil pretreatment on skin tumor initiation in mice. Cancer Res, 29:1773-1780, 1969.
YUSPA, S.H.; HENNINGS, H.; SAFFIOTTI, U. - Cutaneous chemical carcinogenesis: past, present and future. J Invest Dermatol, 67:199-208, 1976. DOI: https://doi.org/10.1111/1523-1747.ep12513040
PELLING, J.C.; ERNST, S.M.; STRAWHECKER, J.M.; JOHNSON, J.A.; NAIRN, R.S.; SLAGA, T.J. – Elevated expression of Ha-ras is an early event in two-stage skin carcinogenesis in SENCAR mice. Carcinogenesis, 7:1599-1602, 1986. DOI: https://doi.org/10.1093/carcin/7.9.1599
PELLING, J.C.; FISCHER, S.M. NEADES, R.; STRAWHECKER, J.; SCHWEICKERT, L. – Elevated expression and point mutation of the Ha-ras proto-oncogene in mouse skin tumors promoted by benzoyl peroxide and other promoting agents. Carcinogenesis, 8:1481-1484, 1987. DOI: https://doi.org/10.1093/carcin/8.10.1481
HARPER, J.R.; REYNOLDS, 5H.; GREENHALGH, D.A.; STRICKLAND, J.E.; LACAL, J.C.; YUSPA, S.H. - Analysis of the rasH oncogene and its p21 product in chemicaily induced skin tumors and tumor-derived cell lines. Carcinogenesis, 8:1821-1825, 1987. DOI: https://doi.org/10.1093/carcin/8.12.1821
YAMASAKI, H.; HOLLSTEIN, M.; MARTEL, N.; CABRAL, J.R.P.; GALENDO, D.; TOMATIS, L. - Transplacental induction of a specific mutation in fetal Ha-ras and its critical role in post-natal carcinogenesis. Int J Cancer, 40:818-822, 1987. DOI: https://doi.org/10.1002/ijc.2910400619
WONG, D.T.W.; GERTZ, R.; CHOW, P. et al – Detection of Ki-ras messenger RNA in normal and chemically transformed hamster oral keratinocytes. Cancer Res, 49:4562-4567, 1989.
WEINBERG, W.C.; MORGAN, D.L.; GEORGE, C.; YUSPA, S.H. - A comparison of interfollicuiar and hair derived cells as targets for the v-rasla oncogene in mouse skin carcinogenesis. Carcinogenesis, 12:1119- 1124, 1991. DOI: https://doi.org/10.1093/carcin/12.6.1119
FÜRSTENBERGER, G.; MARKS, E - Growth stimulation and tumor promotion in skin. J Invest Dematol, 81:157s162s, 1983. DOI: https://doi.org/10.1111/1523-1747.ep12540971
FÜRSTENBERGER, G.; GROSS, M..; MARKS, E - Eicosanoids and multistage carcinogenesis in NMRI mouse skin: role of prostaglandins E and F in conversion (first stage of tumor promotion) and promotion (second stage of tumor promotion). Carcinogenesis, 10.91-96, 1989. DOI: https://doi.org/10.1093/carcin/10.1.91
FÜRSTENBERGER, G.; SCHURICH, B.; KAINA, B.; PETRUVSKA, R.T.; FUSENIG, N.E.; MARKS, F. - Tumor induction in initited mouse skin by phorbol esters and methyl methanesu Ifonate: correlation between chromosomal damage and conversion (stage 1 of tumor promotion') in vivo. Carcinogenesis, 10:749-752, 1989. DOI: https://doi.org/10.1093/carcin/10.4.749
SAFFIOTTI, U.; SCHUBICK, P. - Studies on promoting action in skin carcinogenesis. Nati Cancer lnst Monogr, 10:489-507, 1963.
VAN DUUREN, B.L. - Tumor promoting agents in two stage carcinogenesis. Prog Exp Tumor Res, 11.51-68, 1969.
SCHMIDT, R.J.; EVANS, F.J. - Skin irritant effects of esters of phorbol and related polyols. Arch Toxicol, 44279-289, 1980. DOI: https://doi.org/10.1007/BF00278035
COTTERILL, J.A. - Benzoyl peroxide. Acta Derm Venereol (Stock), Suppl. 89:57-63, 1980.
IARC - Benzoyl peroxide. IARC Monogr Eval Carcinog Risk Chem Hum, 36:267-283, 1985.
DELCLOS, KB.; NAGLE, D.S.; BLUMBERG, P.M. - Specific binding of phorbol ester tumor promoters to mouse skin. Celi, 19:1025-1032, 1980. DOI: https://doi.org/10.1016/0092-8674(80)90093-8
DRIEDGER, P.E.; BLUMBERG, P.M. - Specific binding of phorbol ester tumor promoters. Proc NaU Acad Sci USA, 77567-571, 1980. DOI: https://doi.org/10.1073/pnas.77.1.567
SOLANSKI, V.; SLAGA, T.J. - Specific binding of phorbol ester tumor promoters to intact primary epidermal cells from Sencar mice. Proc Nati Acad Sci USA, 78:2549-2553, 1981. DOI: https://doi.org/10.1073/pnas.78.4.2549
WHELDRAKE, J.F; MARSHALL, J.; RAMLI, J.; MURRAY, A.W. - Skin carcinogenesis and promoter binding characteristics in different mouse strains. Carcinogenesis, 3:805-807, 1982. DOI: https://doi.org/10.1093/carcin/3.7.805
ITAI, A.; KATO, Y.; TOMIOKA, N. et al - A receptor model for tumor promoters: rational superposition of teleocidins and phorbol esters. Proc NatlAcad Sci USA, 853688-3692, 1988. DOI: https://doi.org/10.1073/pnas.85.11.3688
NIEDEL, J.E.; KUHN, L.J.; VANDENBARK, G.R. - Phorbol diester receptor copurifies with protein kinase C. Proc Nati Acad Sci USA, 8036-40, 1983. DOI: https://doi.org/10.1073/pnas.80.1.36
BLUMBERG, P.M.; SHARKEY, N.A.; KÔNIG, G.; JAKEN, S.; LEACH, K.L.; JENG, A.Y. - Phorbol ester
receptors-insights into the initial events in the mechanism of action of the phorbol esters. Int Symp Princess Takamatsu Cancer Res Fund, 14:75-87, 1983.
BLUMBERG, P.M.; JAKEN, 5.; K5NIG, B et al - Mechanism of action of the phorbol ester tumor promoters: specific receptors for lipophilic ligands. Biochem Pharmacol, 33.933-940, 1984. DOI: https://doi.org/10.1016/0006-2952(84)90448-9
HECKER E. - Cell membrane associated protein kinase C as receptor of diterpene ester co-carcinogens of the tumor promoter type and the phenotypc expression of turno rs. Arzneim-Forsch/Drug Res, 35:1890-1903, 1985.
HANSEN, L.A.; MONTEIRO-RIVIERE, N.A.; SMART, R.C. - Differential down-reguiation of epidermal protein kinase C by 12-0-tetradecanoylphorboi-1 3-acetate and diacyiglycerol: association with epidermal hyperpiasia and tumor promotion. Cancer Res, 50:5740-5745, 1990.
BURNS, D.J.; BELL, R.M. - Protein kinase C contains two phorbol ester binding domains. J Biol Chem, 266:18330-18338, 1991. DOI: https://doi.org/10.1016/S0021-9258(18)55274-1
NAKAMURA, Y.; COLBURN, N.H.; GINDHART, T.D. - Role of oxygen in tumor promotion: implication of superoxide anion in promotion of neopiastic transformation in JB-6 celis by TPA. Carcinogenesis, 6:229-235, 1985. DOI: https://doi.org/10.1093/carcin/6.2.229
MARNETT, L.J. - Peroxyl free radicais: potencial mediators of tumor initiation and promotiori. Carcinogenesis, 8:1365-1373, 1987. DOI: https://doi.org/10.1093/carcin/8.10.1365
GIMENEZ-CONTI, 1.; VIAJE, A.; CHESNER, J.; CONTI, C.; SLAGA, T.J. - Induction of short-term markers of tumor promotion by organic peroxides. Carcinogenesis, 12.563-569, 1991. DOI: https://doi.org/10.1093/carcin/12.4.563
DURÁN, H.A.; DE REY, B.M. - Differential oxidative stress induced by two different types of skin tumor promoters, benzoyl peroxide and 1 2-O-tetradecanoyl-phorboI -1 3-acetate. Carcinogenesis, 122047-2052, 1991.
DONNELLY JR., TE.; PELLING, J.C.; ANDERSON, C.L.; DALBEY, D. - Benzoyl peroxide activation of protein kinase C activity in epidermal cell membranes. Carcinogenesis, 8:1871-1874, 1987. DOI: https://doi.org/10.1093/carcin/8.12.1871
KUMAR, R.; HOLIAN, O. - Inhibition of mouse skin protein kinase C by benzoyl peroxide. J Invest Dermatol, 96:490-494, 1991. DOI: https://doi.org/10.1111/1523-1747.ep12470194
BOUTWELL, R.K.; TAKIGAWA, M.; VERMA, A.K.; ASHENDEL, C.L. - Observations on the rnechanism of skin tumor promotion by phorbol esters. Int Symp Princess Takamatsu Cancer Res Fund, 14:177-193, 1983.
SISSKIN, E.E.; GRAY, T; BARRETT, J.C. – Correlation between sensitivity to tumor promotion and sustained epidermal hyperpiasia of mice and rats treated with 12-0-tetradecanoyiphorboi- 13-acetate. Carcinogenesis, 3:403-407, 1982. DOI: https://doi.org/10.1093/carcin/3.4.403
KLEIN-SZANTO, A.J.P.; SLAGA, T.J. - Effects of peroxides on rodent skin: epidermal hyperplasia and tumor promotion. J lnvest Dermatol, 7920-34, 1982. DOI: https://doi.org/10.1111/1523-1747.ep12510444
SLAGA, TJ.; KLEIN-SZANTO, A.J.P. - Initiation-promotion versus complete skin carcinogenesis in mice: importance of dark basai keratinocytes (stem cells). Cancer lnvest, 1:425-436, 1983. DOI: https://doi.org/10.3109/07357908309048511
NAITO, M.; NAITO, Y.; DI GIOVANNI, J. – Comparison of the histological changes in the skin of D13Al2 and C5713L/6 mice following exposure to various promoting agents. Carcinogenesis, 8:1807-1815, 1987. DOI: https://doi.org/10.1093/carcin/8.12.1807
CHOUROULINKOV, I.; LASNE, C.; PHILLIPS, D.; GROVER, P. - Sensitivity of the skin of different mouse strains to the promoting effect of 1 2-O-tetradecanoyi-phorbol-1 3-acetate. Sull Cancer (Paris), 75.557-565, 1988.
CHOUROULINKOV, I.; LASNE, O.; LOWY, R. et al - Dose and frequency effect in mouse skin tumor promotion. Cancer Res, 49:1964-1969, 1989.
SLAGA, TJ.; KLEIN-SZANTO, A.J.P.; TRIPLETT, L.L.; YOTTI, L.P.; TROSKO, J.E. - Skin tumor-promoting activity of benzoyl peroxide, a widely used free radical-generating compound. Science, 2 13:1 023-1025, 1981. DOI: https://doi.org/10.1002/chin.198201338
SISSKIN, E.E.; BARRETT, J.C. - Hyperplasia of Syrian hamster epidermis induced by single but not multiple treatments with 1 2-O-tetradecanoylphorboi-13-acetate. Cancer Res, 41:346-350, 1981.
GOERTTLER, K.; LOEHRKE, H.; SCHWEIZER, J.; HESSE, B. - Positive 2-stage carcinogenesis in female Sprague-Dawley rats using 7,12-dimethyi-benz[a]anthracene as initiator and 1 2-O-tetradecanoyl-phorbol-13-acetate as promoter: results of a pilot study. Virchows Arch A Pathol Anat Histol, 385:181-186, 1980. DOI: https://doi.org/10.1007/BF00427403
SHUBICK, P. - Studies on the promoting phase in the stages of carcinogenesis in mice, rats, rabbits, and guinea pigs. Cancer Res, 10:13-17, 1950.
STENBACK, F. - Skin carcinogenesis as a model system: observations on species, strain, and tissue sesitivity to 7,1 2-dimethyibenz[a]anthracene with or without promotion from croton oh. Acta Pharmacol Toxicol, 46.89-97, 1980. DOI: https://doi.org/10.1111/j.1600-0773.1980.tb02426.x
GOERTTLER, K.; LOEHRKE, H.; HESSE, B.; SCHWEIZER, J. - Skin tumor formation in the European hamster (Cricetus cricetus L) after topicai initiation with 7,12-dhmethyibenz[a]anthracene (DMBA) and promotion with 12-0-tetradecanoyiphorbol-13-acetate (TPA). Carcinogenesis, 5:521-524, 1984. DOI: https://doi.org/10.1093/carcin/5.4.521
ASHMAN, L.K.; MURRAY, A.W.; COOK, M.G.; KOT-LARSKI, 1. - Two-stage skin carcinogenesis in sensitive and resistant mouse strains. Carcinogenesis, 3.99-1 02, 1982. DOI: https://doi.org/10.1093/carcin/3.1.99
REINERS JR., J.J.; NESNOW, S.; SLAGA, TJ. – Murine susceptibhIity to two-stage skin carcinogenesis is influenced by the agent used for promotion. Carcinogenesis, 5.301-307, 1984. DOI: https://doi.org/10.1093/carcin/5.3.301
HENNINGS, H.; DEVOR, D.; WENK, M.L. et al - Comparison of two-stage epidermal carcinogenesis initiated by 7,1 2-dimethylbenz[a]anthracene or N-methyl-N'-nitro-N'nitrosoguanidine in newborn and adult SENCAR and Baib/c mice. Cancer Res, 4 1:773-779, 1981.
FISCHER, S.M.; O'CONNELL, J.E; CONTI, C.J. et al - Characterization of an inbred strain of the SENCAR mouse that is highly sensitive to phorboi esters. Carcinogenesis, 8:42 1 -424, 1987. DOI: https://doi.org/10.1093/carcin/8.3.421
SCHWENTKER, V. - The gerbil. A new laboratory animal. Illinois Vet, 6.5-9, 1963.
HANDLER, A.H.; MAGALINI, Si.; PAV, D. – Oncogenic studies on the Mongolian gerbil. Cancer Res, 26.844-847, 1966.
QUEVEDO JR., W.C.; BIENIEKI, T.C.; FAUSTO, N.; MAGALINI, SI. - induction of pigmentary changes in the skin of the Mongolian gerbil by chemical carcinogens. Experientia, 24:585-586, 1968. DOI: https://doi.org/10.1007/BF02153788
MC DONALD, C.J.; QUEVEDO JR., W.C.; BIENIEKI, TC.; FAUSTO, N. - Role of melanocytes in responses of the skin of Mongolian gerbils to chemical carcinogens. J Invest Dermatol, 54.92, 1970.
WEINSTEIN, I.B.; TROLL, W. - National Cancer institute workshop on tumor promotion and cofactors in carcinogenesis. Cancer Res, 37.3461-3463, 1977.
GUZMAN-SILVA, M.A.; GUIMARAES, J.S.P. – Análise morfológica comparativa da carcinogênese química cutânea entre camundongo (Mus musculus) e gerbil (Meriones unguiculatus). Rev Bras Cancerol, 3231-42, 1986.
GUZMÁN-SiLVA, M.A.; ROSSI, M.i.D.; GUIMARAES, J.S.P. - Estudo do gerbil (Meriones unguiculatus) como modelo em oncologia experimental. 1. indução de neoplasias cutâneas. Rev Bras Cancerol, 32.155, 1986.
GUZMAN-SILVA, M.A.; ROSSI, MW.; GUIMARAES, J.S.P. - Carcinogênese química cutânea e subcutânea em gerbil (Meriones unguiculatus). Acta Oncol Bras, 9/10.56-72, 1989/1990.
LEBLOND, C.P.; WALKER, B.E. - Renewal of cell populations. Physiol Rev, 36:255-275, 1956. DOI: https://doi.org/10.1152/physrev.1956.36.2.255
IVERSEN, OH.; IVERSEN, U.M. - is there a diurnal variation in the susceptibility of mouse skin to the tumorigenic action of methylcholanthrene? A study of tumour yield with special reference to the variation between cages. Acta Path Microbiol Scand (A), 84: 406- 414, 1976. DOI: https://doi.org/10.1111/j.1699-0463.1976.tb00134.x
WRIGHT, N.A.; APPLETON, D.R. - The metáfase arrest technique. A critical review. Cell Tissue Kinet, 13. 643-663, 1980. DOI: https://doi.org/10.1111/j.1365-2184.1980.tb00503.x
CAMPOS, H. - Estatística experimental não-paramétrica. 4 ed. Piracicaba: USP, 113-134; 202-211; 234-243, 1983.
SETÂLÂ, K.; MERENMIES, L.; STJERNVALL, L.; AHO, Y.; KAJANNE, P. - Mechanism of experimental tumorigenesis. 1. Epidermal hyperplasia in mouse caused by locally applied tumor initiator and dipole-type tumor promoter. JNCI, 23.925-951, 1959.
TARIN, D. - Sequential electron microscopical study of experimental mouse skin carcinogenesis. Int J Cancer, 2:195-211, 1967. DOI: https://doi.org/10.1002/ijc.2910020302
RAICK, A.N. - Ultrastructural, histological and biochemical alterations, produced by 1 2-O-tetradecanoylphorbol-13-acetate on mouse epidermis and their relevance to skin tumor promotion. Cancer Res, 33269-286, 1973.
SETALA, K.; MERENMIES, L.; STJERNVALL, L.; NYHOLM, M. - Mechanism of experimental tumorigenesis. IV. Ultrastructure of interíollicuiar epidermis of normal adult mouse. JNCI, 24.329-353, 1960.
POUND, A.W. - Carcinogenesis and celi proliferation. N Z Med J, 67:88-99, 1968.
RAICK, A.N.; THUMM, K.; CHIVERS, B.R. - Early effects of 12-0-tetradecanoylphorboi-1 3-acetate on the incorporation of tritiated precursors into DNA, and the thickness of the interfollicular epidermis, and their relation to tumor promotion in mouse skin. Cancer Res, 32:1562-1568, 1972.
RAICK, A.N.; BURDZY, K. - Ultrastructural and biochemical changes induced in mouse epidermis by a hyperplastic agent, ethylphenyipropiolate. Cancer Res, 33:2221-2230, 1973.
RÁICK, A.N. - CelI proliferation and promoting action in skin carcinogenesis. Cancer Res, 34.920-926, 1974.
ARGYRIS, T.S. - Epidermal growth following a single application of 12-0-tetradecanoylphorboi-13-acetate in mice. Am J Pahol, 98.539-648, 1980.
ARGYRIS, T.S. - The nature of the epidermal growth produced by the first application of 1 2-O-tetradecanoyl-phorbol-13-acetate on the skin of mice initiated with dimethyibenzanthracene. J lnvest Dermatol, 77230-234, 1981. DOI: https://doi.org/10.1111/1523-1747.ep12480059
ARGYRIS, T.S. - Nature of the epidermal hyperplasia produced by mezerein, a weak tumor promoter, in initiated skin of mice. Cancer Res, 43:1768-1773, 1983.
HASPER, F.; MÜLLER, G.; SCHWEIZER, J. - Histological, proliferative, and biochemical alterations in dorsal epidermis of the Syrian golden hamster induced by of 12-0-tetradecanoy1phorboi-13-acetate and the calcium ionophore A23187. Cancer Res, 422034-2039, 1982.
ALDAZ, CM.; CONTI, C.J.; GIMÉNEZ, l.B.; SLAGA, TJ.; KLEIN-SZANTO, A.J.P. - Cutaneous changes during prolonged application of TPA on mouse skin and residual effects after cessation of treatment. Cancer Res, 452753-2759, 1985.
POTTEN, C.S. - Celi repiacement in epidermis (keratopolesis) via discrete units of proliferation. Int Rev Cytol, 69271-318, 1981. DOI: https://doi.org/10.1016/S0074-7696(08)62326-8
BERENBLUM, I.; SHUBICK, P. - The role of croton ou applications, associated with a single painting of carcinogen, in tumor induction of the mouse's skin. Br J Cancer, 1.379-382, 1947. DOI: https://doi.org/10.1038/bjc.1947.35
BERENBLUM, 1.; SHUBICK, P. - A new, quantitative approach to the study of the stages of chemical carcinogenesis in mouse's skin. Br J Cancer, 1.383-391, 1947. DOI: https://doi.org/10.1038/bjc.1947.36
FREI, J.V.; STEPHENS, P. -- The correlation of promotion of tumour growth and of induction of hiperplasia in epidermal two-stage carcinogenesis. Br J Cancer, 22.53-89, 1968. DOI: https://doi.org/10.1038/bjc.1968.12
BERENBLUM, 1. - The coccarcinogenic action of cróton resin. Cancer Res, 1:44-48, 1941.
SALAMAN, M.H.; GWYNN, R.H. - The histology of co-carcinogenesis in mouse skin. Br J Cancer, 5.252- 263, 1951. DOI: https://doi.org/10.1038/bjc.1951.26
HENNINGS, H.; BOUTWELL, R.K. - Studies on the mechanism of skin tumor promotion. Cancer Res, 30312-320, 1970.
WALTERS, M.A.; ROE, F.J.C. - The induction of tumors in mice by neonatai injectiori of 9,10-dimethyi-1,2-benzanthracene (DMBA) followed by appiications of croton oil to the skin. Br J Cancer, 21.358-366, 1967. DOI: https://doi.org/10.1038/bjc.1967.41
KRUEGER, G.G.; CHAMBERS, D.A.; SHELBY, J. - Epidermal proliferation of nude mouse skin, pig skin and pig skin grafts. Failure of nude mouse skin to respond to the tumor promoter 1 2-O-tetradecanoylphorbol-13-acetate. J Exp Med, 152:1329-1333, 1980. DOI: https://doi.org/10.1084/jem.152.5.1329
BERKELHAMMER, J.; OXENHANDLER, R.W. - Evaluation of premalignant and malignant lesions during the induction of mouse melanomas. Cancer Res, 471251-1254, 1987.
B0URIN, M. C.; DELESCLUSE, C.; FÜRSTENBERGER, G. et al - Effect of phorbol esters on guinea pig skin in vivo. Carcinogenesis, 3.671-676, 1982. DOI: https://doi.org/10.1093/carcin/3.6.671
VAN DUUREN, B.L.; SIVAK, A.; SEGAL, A.; SEIDMAN, I.; KATZ, C. - Dose-response studies with a pure tumor promoting agent, phorbol myristate acetate. CancerRes, 332166-2172, 1973.
BURNS, F.J.; VANDERLMN, M; SIVAK,A.; ALBERT, R.E. - Regression kinetics of mouse skin papillomas. Cancer Res, 36:1422-1427.
REDDY, A.L.; CALDWELL, M; FIALKOW, P.J. - Sequential studies of skin tumorigenesis in phos-phogiyceratekinase mosaic mice: effect of resumption of promotion on regressed papiliomas. Cancer Res, 47:1947-1951.
VAN DUUREN, B.L.; SIVAK, A. - Tumor-promoting agents from Croton tiglium L. and their mode of action. Cancer Res, 28:2349-2356, 1968.
Dl GIOVANNI, J.; WALKER, S.C.; BELTRAN, L.; NAITO, M.; EASTIN JR, W.C. - Evidence for a common genetic pathway controlling susceptibility to mouse skin tumor promotion by diverse classes of promoting agents. Cancer Res, 51.1398-1405, 1991.
GOERTRLER, K.; LOEHRKE, H.; SCHWEIZER, J.; HESSE, B. - Two-stage tumorigenesis of dermal melanocytes in the back skin of the Syrian Golden hamster using systemic initiation with 7,12-dimethylbenz[a]anthracene and topicai promotion with 12-0-tetradecanoyiphorboI-1 3-acetate. Cancer Res, 40:155- 161, 1980.
SCHWEIZER, J.; LOEHRKE, H.; EDLER, L.; GOERTTLER, K. - Benzoyl peroxide promoters the formation of melanotic tumors in the skin of 7,12-dimethylbenz[a]anthracene-initiated Syrian Golden hamsters. Carcinogenesis, 8:479-482, 1987. DOI: https://doi.org/10.1093/carcin/8.3.479
YUSPA, S.H.; BEN, T.; HENNINGS, H.; LICHTI, U. - Divergent responses in epidermal basal cells exposed to the tumor promoter TPA. Cancer Res, 422344-2349, 1982.
YUSPA, S.H.; KULESZ-MARTIN, M.; BEN, T.; HENNINGS, H. - Transformation of epidermal cells in culture. J Invest Dermatol, 81:162s168s, 1983. DOI: https://doi.org/10.1111/1523-1747.ep12540999
YUSPA, S.H. - Mechanisms of initiation and promotion in mouse epidermis. IARC Sci Pubi, 56:191 -204, 1984.
COLBURN, N.H.; FARBER, E.; WEINSTEIN, I.B.; DIAMOND, L.; SLAGA, T.J. - American Cancer Society workshop on tumor promotion and antipromotion. Cancer Res, 47, 5509-55 13, 1987.
TRAINlN, N. - Adrenal imbalance in mouse skin carcinogenesis. Cancer Res, 23:415-419, 1963.
VIAJE, A.; SLAGA, TJ.; WIGLER, M.; WEINSTEIN, I.B. - Effects of anti-infiammatory agents on mouse skin tumor promotion epidermal DNA synthesis, phorbol ester-induced cellular proliferation, and production of plasminogen activator. Cancer Res, 37:1530-1536, 1977.
SLAGA, T.J. - Anti-infiammatory steroids: potent inhibitors of tumor promotion. In: SLAGA, TJ, ed. Modifiers of chemical carcinogenesis: an approach to the biochemical mechanism and cancer prevention. New York: Raven Press, 1980, 111-126.
SLAGA, TJ.; KLEIN-SZANTO, A.J.P.; FISCHER, S.M.; WEEKS, C.E.; NELSON, K.; MAJOR, S. - Studies on mechanism of action of anti-tumor-promoting agents: theis specificity in two-stage promotion. Proc Natl Acad Sci USA, 77:2251-2254, 1980. DOI: https://doi.org/10.1073/pnas.77.4.2251
DAVIDSON, K.A.; SLAGA, T.J. - Effects of phorbol ester tumor promoters and hyperpiasiogenic agents on cytopiasmic glucocorticoid receptors in epidermis. J Invest Dermatol, 79378-382, 1982. DOI: https://doi.org/10.1111/1523-1747.ep12529883
DAVIDSON, K.A.; SLAGA, T.J. - Glucocorticoid receptor leveis in mouse skin after repetititve applications of TPA and mezerein. Cancer Res, 433847-3851, 1983.
SLAGA, TJ.; BOWDEN, G.T.; BOU1WELL, R.K. - Acetic acid, a potent stimuiator of mouse epidermal macromoiecular synthesis and hyperplasia but with weak tumor-promoting ability. JNCI, 55.983-987, 1975. DOI: https://doi.org/10.1093/jnci/55.4.983
SLAGA, TJ.; LICHTI, U.; HENNINGS, H.; ELGJO, K.; YUSPA, S.H. - Effect of tumor promoters and steroidal anti-inflammatory agents on skin of newborn mice in vivo and in vitro. JNCI, 60:425-431, 1978. DOI: https://doi.org/10.1093/jnci/60.2.425
SHAVIT, Y.; TERMAN, G.W.; MARTIN, F.C.; LEWIS, J.W.; LIEBESKIND, J.C.; GALE, R.P. - Stress, opioid peptides, the immune system, and cancer. J ImmunoI, 135:834-837s, 1985.
SCRIBNER, J.D.; SUSS, R. - Tumor initiation and promotion. Int Rev Exp Pathol, 18:137-198, 1978.
FENSKE, M. - Production of steroids by in vitro superfusion from adrenals of the Mongolian gerbil (Meriones unguiculatus): effect of acute stress. Comp Biochem Physiol [A], 74.971-976, 1983. DOI: https://doi.org/10.1016/0300-9629(83)90379-1
BOUTWELL, R.K. - On the role of tumour promotion in chemical carcinogenesis. IARC Sci Publ, 563-11, 1984.
MITIDIERI, F.M.A.; SANTOS, R.O.J.; POPOLO, A.C. et al - Superoxide dismutase and xanthine oxidase in gerbil skin. In: Reunião Anual da Sociedade Brasileira de Bioquímica e Biologia Molecular, XX1234, 1992.
SANTOS, R.O.J.; POPOLO, A.C.; GUZMAN-SILVA, M.A.; AFFONSO, O.R.; MITIDIERI, F.M.A. - Efeito de iniciador e promotor tumoral na atividade xantina desidrogenase e xantina oxidase em pele de camundongo e de gerbil. In: Reunião Anual da Federação de Sociedades de Biologia Experimental, VIll330, 1993.
POPOLO, A.C.; SANTOS, R.O.J.; GUZMAN-SILVA, M.A.; AFFONSO, O.R.; MITIDIERI, F.M.A. - Estudo comparativo de dois tipos de promotor tumoral na atividade xantina oxidase de pele de gerbil. In: Reunião Anual da Federação de Sociedades de Biologia Experimental, VlIl330, 1993.
