Análise Morfológica Comparativa da Carcinogênese Química Cutânea entre Camundongo (Mus Musculus) e Gerbilho (Meriones Unguiculatos)
DOI:
https://doi.org/10.32635/2176-9745.RBC.1986v32n1.3232Palabras clave:
Carcinogênese Química Cutânea, Modelo Cumulativo, Modelo Bifásico, GerbilhoResumen
Foi estudada a resposta da pele de gerbilho à indução química de tumores, comparando-se as alterações morfológicas iniciais com aquelas que ocorrem na pele do camundongo. Dois modelos de carcinogenese foram aplicados: o cumulativo, utilizando metilcolantreno e o bifásico com metilcolantreno como iniciador e óleo de cróton como promotor. As alterações macroscópicas tais como espessamento da pele e hiperemia, induzidas com os dois tratamentos mencionados foram menos evidentes no gerbilho. A reação inflamatória e a hiperplasia, observadas microscopicamente, também foram de menor intensidade na pele de gerbilho, notando-se, durante os dois tratamentos, o paradoxo do estímulo permanente da proliferação celular, evidenciado pela elevação do índice mitotico, sem hiperplasia progressiva da epiderme. A nível ultra-estrutural, com o modelo cumulativo, na epiderme interfolicular do gerbilho, ocorreu dilatação do espaço intercelular menos evidente do que a registrada na do camundongo, e a indução de "células escuras" não foi observada até a 10ª semana de tratamento. Com o modelo bifásico, na epiderme interfolicular do gerbilho, nao houve indução de "células escuras" e a dilatação do espaço intercelular foi inicialmente, mímima, deixando de existir posteriormente, apesar da continuidade do tratamento. A pele do gerbilho, quando comparada com a de camundongo, mostrou-se relativamente resistente a carcinogenese química. Se no camundongo, com o modelo bifásico, após um período de latência de sete semanas, houve a formação de vários papilomas, no gerbilho não houve desenvolvimento de tumor até à 304 semana, com o modelo cumulativo, tanto no camundongo como no gerbilho, houve desenvolvimento de um papiloma; o período de latência no camundongo foi de dez semanas, enquanto que no gerbilho foi de quinze semanas. Os resultados obtidos sugerem que a relativa resistência da pele de gerbilho à carcinogênese química parece residir em um fenômeno de adaptação ao processo de promoção tumoral, particularmente com óleo de cróton.
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Becker FF. Recent concepts of initiation and promotion in carcinogenesis. Am. J. Pathol. 1981,-105(1): 3-9.
Boutwell RK. Some biological aspects of skin carcinogenesis. Prog. exp. Tumor Res. 1964; 4: 207-250. DOI: https://doi.org/10.1159/000385978
Boutwell RK, Verma AK, Ashendel CL, Astrup E. Mouse skin: a usefui model system for studying the mechanism of Chemical carcinogenesis. Carcinog. Compr. Surv. 1982; 7:1-12.
Guzmán Silva MA, Guimarães JSP. Carcinogênese química cutânea. Rev. Bras. Cancerol. 1985; 31: 285-291.
Ryses HJP. Chemical carcinogenesis. New Engl. J. Med. 1971; 285 (13): 721-734. DOI: https://doi.org/10.1056/NEJM197109232851305
Scribner JD, Süss R. Tumor initiation and promotion. Int. Rev. exp. Pathol. 1978; 18: 137-198.
Slaga TJ, Fischer SM, Weeks CE, Klein-Szanto AJP, Reiners J. Studies on the mechanism involved in multistage carcinogenesis in mouse skin. J. cell. Biochem. 1982;18(1): 99-119. DOI: https://doi.org/10.1002/jcb.1982.240180109
Slaga TJ, Fischer SM, Weeks CE, Nelson K, Mamrack M, Klein-Szanto AJP. Specificity and mechanism(s) of promoter inhibitors in multistage promotion. Carinog. Compr. Surv. 1982; 7: 19-34.
Slaga TJ, Klein-Szanto AJP. Initiation-promotion versus complete skin carcinogenesis in mice: importance of dark basal Keratinocytes (stem cells). Cancer Invest 1983;1(5): 425-436. DOI: https://doi.org/10.3109/07357908309048511
Weinstein IB, Troll W. National Câncer Institute workshop on tumor promotion and cofactors in carcinogenesis. Cancer Res. 1977; 37: 3461-3463.
Yuspa SH, Hennings H, Saffiotti U. Cutaneous Chemical carcinogenesis: past, present and future. J. Invest. Dermatol. 1976; 67: 199-208. DOI: https://doi.org/10.1111/1523-1747.ep12513040
Ashman LK, Murray AW, Cook MG, Kotiarski I. Two-stage skin carcinogenesis in sensitive and resistant mouse strains. Carcinogenesis 1982; 3(1): 99-102. DOI: https://doi.org/10.1093/carcin/3.1.99
Di Giovanni J. Slaga TJ, Juchau MR. Comparativa epidermal metabolism of mice with differing sensitivity to skin tumori-genesis by DMBA. Proc. Am. Assoe. Câncer Res. 1979; 20: 134.
Hennings H, Devor D, Wenk ML, et al. Comparison of two-stage epidermal carcinogenesis initiated by 7-12-dimethyl-benz(a) — anthracene of N-methyl-N'-nitro-N-nitrosoguanidine in newborn and adult SENCAR and BALB/c mice. Cancer Res. 19’81; 41:773-779.
Legraverend C, Mansour B, Nebert DW, Holland JM. Genetic differences in benzo(a)pyrene-initiated tumorigenesis in mouse skin. Pharmacology 1980; 20 (5): 242-255. DOI: https://doi.org/10.1159/000137370
Shubick P. Studies on the promoting phase in the stages of carcinogenesis in mice, rats, rabbits and guinea pigs. Cancer Res. 1950; 10:13-17.
Sisskin EE, Gray T, Barrett JC. Correlation between sensitivity to tumor promotion and sustained epidermal hyperplasia of mice and rats treated with 12-0-tetradecanolyphor-bol-13-acetate. Carcinogenesis 1982; 3 (4): 403-407. DOI: https://doi.org/10.1093/carcin/3.4.403
Stenbáck F. Skin carcinogenesis as a model system: observations on species strain and tissue sensitivity to 7,12-dime-thylbenz (a) anthracene with or without promotion from crotonoil. Acta Pharmacol. Toxicol. 1980: 46(2): 89-97. DOI: https://doi.org/10.1111/j.1600-0773.1980.tb02426.x
Salaman MH, Roe FJC. Cocarcionigenesis. Br. med. Bull. 1964; 20 (21:139-144. DOI: https://doi.org/10.1093/oxfordjournals.bmb.a070307
Fischer SM, Gleason, GL, Bohrman JS, Slaga TJ. Prostaglandin enhancement of skin tumor initiation and promotion. Adv. Prostaglandin Thromboxane Res. 1980; 6: 517-522.
Frei JV, Stephens P. The correlation of promotion of tumor growth and of induction of hyperplasia in epidermal two-stage carcinogenesis. Br. J. Cancer 1968; 22: 83-92. DOI: https://doi.org/10.1038/bjc.1968.12
Fürstenberger G, Berry DL, Sorg B, Marks F. Skin tumor promotion by phorbol esters is a two-stage process. Proc. Natl. Acad. Sci. USA 1981; 78(12) .7722-7726. DOI: https://doi.org/10.1073/pnas.78.12.7722
Fürstenberger G, Sorg B, Marks F. Tumor promotion by phorbol esters in skin: evidence for a memory effect. Science 1983; 220: 89-91. DOI: https://doi.org/10.1126/science.6828884
Pound AW. Carcinogenesis and cell proliferation. N.Z. med. J. 1968; 67: 88-99.
Setalà K, Merenmies L, Stjernvall L, Aho Y, Kajanne P. Mechanism of experimental tumorigenesis. I . Epidermal hyperplasia in mouse caused by locally applied tumor initiator and dipole-type tumor promoter. J. Natl. Cancer Inst. 1959; 23.925-951.
Slaga TJ, Fischer SM, Weeks CE, Klein-Szanto AJP. Multistage Chemical carcinogenesis in mouse skin. Curr. Probl. Dermatol. 1980; 10: 193-218. DOI: https://doi.org/10.1159/000396290
Berenbium I. A speculative review; the probable nature of promoting action and its significance in the understanding of the mechanism of carcinogenesis. Cancer Res. 1954; 14(7): 471-477.
Setälä' K, Merenmies L, Niskanen EE, Nyholm M, Stjern vall L. Mechanisms of experimental tumorigenesis. VI. Ultrastructural alterations in mouse epidermis caused by locally applied carcinogen and dipole-type tumor promoter. J. Natl. Cancer Inst. 1960; 25: 11 55-1189.
Raick AN, Ritchie AC. The fine structural changes induced in the epidermis by croton oil fraction Aj and two stage carcinogenesis in mouse skin. Proc. Am. Assoe. Cancer Res. 197.1; 12:66.
Klein-Szanto AJP, Slaga TJ. Numerical variation of dark cells in normal and chemically induced hyperplastic epidermis with age of animal and efficiency of tumor promoter. Cancer Res. 1981; 41 (11 Parti): 4437-4440.
Raick AN. Ultrastructural, histological and biochemical alterations produced by 12-0-tetradecanoylphorbol-13-acetate on mouse epidermis and their relevance to skin tumor promotion. Câncer Res. 1973; 33: 269-286.
Raick AN. Cell differentiation and tumor-promoting action in skin carcinogenesis. Cancer Res. 1974; 34: 291 5-2925.
Schwentker V. The gerbil. A new laboratory animal. Illinois Vet. 1963; 6: 5-9.
Handler AH, Magalini SI, Pav D. Oncogenic studies on the Mongolian gerbil. Cancer Res. 1966; 26: 844-847.
McDonald CJ, Quevedo Jr. WC, Bienieki TC, Fausto N. Role of melanocytes in responses of the skin of Mongolian gerbils to Chemical carcinogens. J. Invest. Dermatol. 1970; 54 92.
Quevedo Jr WC, Bienieki TC, Fausto N, Magalini SI. Induction of pigmentary changes in the skin of the Mongolian gerbil by Chemical carcinogens. Experientia 1968; 24: 585-586. DOI: https://doi.org/10.1007/BF02153788
Van Duuren BL. Tumor promoting agents in two-stage carcinogenesis. Prog. exp. Tumor Res. 1969; 11 :51-68.
Burke TJ. Rats, mice, hamsters and gerbils. Vet. Clin. North Am.: Small Anim. Pract. 1979; 9(3): 473-486. DOI: https://doi.org/10.1016/S0195-5616(79)50057-6
Behmer OA, Castro de Tolosa EM, Freitas Neto AG. Manual de técnicas para histologia normal e patológica. São Paulo: EDART-EDUSP, 1976: 117.
Pearse AGE. Histochemistry. Theoretical and applied 2nd ed. London: J & A. ChurchilI Ltd., 1960: 919.
Zugibe FT. Diagnostic histochemistry. Saint Louis: C. V. Mosby Company, 1970: 257.
Humphrey CD, Pittman FE. A simple methylene blue-azure II — basib fuchsin stain for epoxy-embebbed tissue sections. Stain Technol. 1974:49(1):9-14. DOI: https://doi.org/10.3109/10520297409116929
Reynolds ES. The use of lead citrate at high pH as an electron-opaque stain in electron microscopy. J. Cell Biol. 1963; 17:208-212. DOI: https://doi.org/10.1083/jcb.17.1.208
Strauss JS, Matoltsy AG. Pele. In: Weiss L, Greep RO. Histologia. 4. ed. Rio de Janãiro: Guanabara Koogan, 1981: 501.
Berenbium I, Shubick P. A new, quantitative approach to the study of the stages of Chemical carcinogenesis in mouse's skin. Br. J. Cancer 1947; 1 ; 383-391. DOI: https://doi.org/10.1038/bjc.1947.36
Tarin D. Sequential electron microscopical study of experimental mouse skin carcinogenesis. Int. J. Cancer 1967; 2: 195-211. DOI: https://doi.org/10.1002/ijc.2910020302
Setälä K, Merenmies L, Stjernavall L, Nyholm M. Mechanism of experimental tumorigenesis. IV. Ultrastrueture of interfollicular epidermis of normal adult mouse. J. Natl. Cancer Inst. 1960; 24: 329-353.
Lever WF. Histopathology of the skin. 5th ed. Philadelphia: JB Lippincott Company, 1975: 9-45.
Argyris TS. Epidermal growth following a single application of 12-0-tetradecanoylphorbol-13-acetate in mice. Am J. Pathol. 1980: 98(3) 639-648.
Raick AN, Thumm K, Chivers BR. Early effects of 12-0-tetradecanoylphorbol-13-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. Câncer Res. 1972; 32:1 562-1 568.
Fenske M. Produetion of steroids by in vitro superfusion from adrenals of the Mongolian gerbil (Meriones unguiculatus): effect of acute stress. Comp. Biochem. Physiol. lAI 1983; 74(4)971-976. DOI: https://doi.org/10.1016/0300-9629(83)90379-1
Quevedo Jr. WC, Fleischmann RD, Dyckman J, Jimbow K, Bienieki TC. Ultrastructural observations on DMBA-induced dermal hyperpigmentation and blue nevus-like tumors in the Mongolian gerbil. Proc. Soc. exp. Biol. Med. 1980; 163(4) :461-468. DOI: https://doi.org/10.3181/00379727-163-40797
