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Induction of the deficient acid DNAse activity in mouse interfollicular epidermis by croton oil as a possible tumor promoting mechanism

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Summary

Histochemical activity of acid DNAse, intensity of nucleic acid staining and histological alterations in mouse interfollicular epidermis (I.F.E.) were investigated after a single dose or after chronic topical administration of two hyperplastic agents, of which one (croton oil) was a potent tumor promotor, and the other one (podophyllin) did not promote skin carcinogenesis. Podophyllin induced intense uniform I.F.E. hyperplasia without any proliferation of poorly differentiated basal cells, without increased nucleic acid staining and without any appreciably decreased acid DNAse activity. On the other hand, croton oil (as well as TPA) produced almost immediate, distinct hyperplasia of poorly differentiated basal cells with increased intensity in the staining of both nucleic acids and nearly complete deficiency in acid DNAse activity. Similar histochemical and histological patterns were observed at the sites of wounding hyperplasia in untreated control mice. Such wounding hyperplasia was thought also to be a tumor promoting factor. It was suggested that the decrease in acid DNAse activity which occured almost immediately after administration of potent tumor promotors and which could not be induced by a hyperplastic agent without tumor promoting action may have a particular importance in the mechanisms of tumor promotion.

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References

  • Aronson,J., Hempelmann,L.H., Okada,S.: Preliminary studies on the histological demonstration of deoxyribonuclease II by adaptation of the Gomori acid phosphatase method. J. Histochem. Cytochem. 6, 255–259 (1958)

    Google Scholar 

  • Baird,W.M., Sedgwick,J.A., Boutwell,R.K.: Effects of phorbol and four diesters of phorbol on the incorporation of tritiated precursors into DNA, RNA and protein in mouse epidermis. Cancer Res. 31, 1434–1439 (1971)

    Google Scholar 

  • Berenblum,I.: The mechanism of carcinogenesis: A study of the significance of cocarcinogenic action and related phenomena. Cancer Res. 1, 807–814 (1941)

    Google Scholar 

  • Berenblum,I.: A speculative review: The probable nature of promoting action and its significance in the understanding of the mechanism of carcinogenesis. Cancer Res. 14, 471–477 (1954)

    Google Scholar 

  • Berenblum,I.: Carcinogenesis as a biological problem. In: E.Neuberger, El.L.Tatum (Eds.): Frontiers of biology Vol. 34, pp. 1–376. Amsterdam, Oxford: North-Holland Publ. Co 1974

    Google Scholar 

  • Bowden,G.T., Boutwell,R.K.: Studies on the role of stimulated epidermal DNA synthesis in the initiation of skin tumors in mice by N-methyl-N′nitro-N-nitrosoguanidine. Cancer Res. 34, 1552–1563 (1974)

    Google Scholar 

  • Brachet,J.: La détection histochimique des acides pentose nucléiques. C.R. Soc. Biol. (Paris) 133, 88 (1940)

    Google Scholar 

  • Daoust,R., Cantero,A.: The distribution of deoxyribonuclease in normal, cirrhotic and neoplastic rat livers. J. Histochem. Cytochem. 7, 139–143 (1959)

    Google Scholar 

  • Daoust,R., Amano,H.: Ribonuclease and deoxyribonuclease activities in experimental and human tumors by the histochemical substrate film method. Cancer Res. 23, 131–134 (1963)

    Google Scholar 

  • Fort,L., Taper,H.S.: L'activité histochimique des nucléases alcalines et acides, comparée à l'incidence des carcinomes dans le système digestif du rat. Path. Europ. 4, 43–57 (1969)

    Google Scholar 

  • Fort,L., Taper,H.S., Brucher,J.M.: Nucleases activity in different segments of the human digestive tube compared to the incidence of carcinomas. (Histochemical study). Histochem. 20, 150–158 (1969)

    Google Scholar 

  • Fort,L., Taper,H.S., Brucher,J.M.: Morphological alterations and focal deficiency of the histochemical activity of acid and alkaline nucleases in rat liver after chronic administration of phenobarbital. Beitr. Path, (in press)

  • Frankfurt,O.S., Raitcheva,E.: Fast onset of DNA synthesis stimulated by tumor promoter in mouse epidermis at the initiation stage of carcinogenesis. J. nat. Cancer Inst. 51, 1861–1864 (1975)

    Google Scholar 

  • Friedewald,W.F., Rous,P.: The initiating and promoting elements in tumor production. An analysis of the effects of tar, benzpyrene and methylcholanthrene on rabbit skin. J. exp. Med. 50, 101–126 (1944)

    Google Scholar 

  • Gaudin,D., Gregg,R.S., Yielding,K.L.: DNA repair inhibition: a possible mechanism of action of cocarcinogens. Biochem. biophys. Res. Commun. 45, 630–636 (1971)

    Google Scholar 

  • Gaudin,D., Gregg,R.S., Yielding,K.L.: Inhibition of DNA repair by cocarcinogens. Biochem. biophys. Res. Commun. 48, 945–949 (1972)

    Google Scholar 

  • Godlewski,H., Vorbrodt,A.: Przystosowanie melody Bracheta do histochemicznego wykrywania Kwasow nukleinowych. Folia morph. (Warszawa) 5, 137–142 (1954)

    Google Scholar 

  • Gwynn,R.H., Salaman,M.H.: Studies on cocarcinogenesis. SH-factors and other substances tested for co-carcinogenic action in mouse skin. Brit. J. Cancer 7, 482–489 (1954)

    Google Scholar 

  • Hennings,H., Boutwell,R.K.: Studies on the mechanism of skin tumor promotion. Cancer Res. 30, 312–320 (1970)

    Google Scholar 

  • Langenbach,R., Kuszynski,C.: Nonspecific inhibition of DNA repair by promoting and nonpromoting phorbol esters. J. nat. Cancer Inst. 55, 801–802 (1975)

    Google Scholar 

  • Lester,S.K., Cauldwell,E.W.: Effect of podophyllin on mouse skin. II. Consideration of some functional aspects. J. nat. Cancer Inst. 10, 131–145 (1949)

    Google Scholar 

  • Mottram,J.C.: A developing factor in experimental blastogenesis. J. Path. Bact. 56, 181–187 (1944)

    Google Scholar 

  • Paul,D.: Effects of carcinogenic, noncarcinogenic and cocarcinogenic agents on the biosynthesis of nucleic acids in mouse skin. Cancer Res. 29, 1218–1225 (1969)

    Google Scholar 

  • Paul,D., Hecker,E.: On the biochemical mechanism of tumorigenesis in mouse skin. II. Early effects on the biosynthesis of nucleic acids induced by initiating doses of DMBA and promiting doses of phorbol-12,13-diester TPA. Z. Krebsforsch. 73, 149–163 (1969)

    Google Scholar 

  • Peraino,C., Fry,R.J., Staffeld,E., Kisieleski,W.E.: Effect of varying the exposure to phenobarbital on its enhancement of 2-acethylaminofluorene induced hepatic tumorigenesis in the rat. Cancer Res. 33, 2701–2705 (1973)

    Google Scholar 

  • Poirier,M.C., De Cicco,B.T., Lieberman,M.W.: Non specific inhibition of DNA repair synthesis by tumor promotors in human diploid fibroblasts damaged with N-acetoxy-2-acetylaminofluorene. Cancer Res. 35, 1391–1397 (1975)

    Google Scholar 

  • Raick,A.N.: Studies on the mechanism of skin tumor promotion. The role of cell proliferation and epidermal hyperplasia. Proc. Amer. Ass. Cancer Res. 13, 39 (1972)

    Google Scholar 

  • Raick,A.N.: Ultrastructural, histological and biochemical alterations produced by 12-O-tetradecanoyl-phorbol-13-acetate on mouse epidermis and their relevance to skin tumor promotion. Cancer Res. 33, 269–289 (1973)

    Google Scholar 

  • Raick,A.N.: Cell proliferation and promoting action in skin carcinogenesis. Cancer Res. 34, 920–926 (1974a)

    Google Scholar 

  • Raick,A.N.: Cell differentiation and tumor-promoting action in skin carcinogenesis. Cancer Res. 34, 2915–2925 (1974b)

    Google Scholar 

  • Rohrschreiber,L.R., Boutwell,R.K.: The early stimulation of phospholipid metabolism by 12-O-tetradecanoyl-phorbol-13-acetate and its specificity for tumor promotion. Cancer Res. 33, 1945–1952 (1973)

    Google Scholar 

  • Rous,P., Kidd,J.G.: Conditional neoplasms and subthreshold neoplastic states. J. exp. Med. 73, 365–390 (1941)

    Google Scholar 

  • Saffiotti,U., Shubik,P.: Studies on promoting action in skin carcinogenesis. Nat. Cancer Inst. Monogr. 10, 489–507 (1963)

    Google Scholar 

  • Setälä,K., Merenmies,M., Stjernvall,L., Aho,Y., Kajanne,P.: Mechanisms of experimental tumorigenesis. I. Epidermal hyperplasia in mouse caused by locally applied tumor initiator and dipole-type tumor promotor. J. nat. Cancer Inst. 23, 925–951 (1959)

    Google Scholar 

  • Sivak,A., Ray,F., Van Duuren,B.L.: Phorbol ester tumor-promoting agents and membrane stability. Cancer Res. 29, 624–630 (1969)

    Google Scholar 

  • Taper,H.S., Brucher,J.M.: Die Aktivität der Nucleasen im Zentralnervensystem der Ratte. Acta Neuropath. (Berl.) 12, 42–49 (1969)

    Google Scholar 

  • Taper,H.S., Brucher,J.M., Doyen,G.: Histochemical study on alkaline and acid nucleases activity in the human brain compared to the incidence of malignant tumors. J. neurol. Sci. 12, 369–382 (1971a)

    Google Scholar 

  • Taper,H.S., Fort,L., Brucher,J.M.: Histochemical activity of alkaline and acid nucleases in the rat liver parenchyma during the N-nitrosomorpholine carcinogenesis. Cancer Res. 31, 913–916 (1971b)

    Google Scholar 

  • Taper,H.S., Brucher,J.M., Fort,L.: Activity of alkaline and acid nucleases in tumors of the human central nervous system. Histochemical study. Cancer (Philad.) 28, 482–490 (1971c)

    Google Scholar 

  • Taper,H.S.: The relation between the histochemical activity of nucleases and neoplasms in rat an man. Louvain, Vander (1975)

  • Teebor,G.W., Duker,N.J., Ruacan,S.A., Zachary,K.J.: Inhibition of thymine dimer excision by the phorbol ester phorbol myristate acetate. Biochem. biophys. Res. Commun. 50, 66–70 (1973)

    Google Scholar 

  • Van Duuren,B.L., Sivak,A., Segal,A., Seidman,I., Katz,C.: Dose-response studies with a pure tumorpromoting agent phorbol myristate acetate. Cancer Res. 33, 2166–2172 (1975)

    Google Scholar 

  • Vorbrodt,A.: Histochemical studies on the intracellular localization of acid deoxyribonuclease. J. Histochem. Cytochem. 9, 647–655 (1961)

    Google Scholar 

  • Wachstein,M., Meisel,R.: Histochemistry of hepatic phosphatases at a physiologic pH. Amer. J. clin. Path. 27, 13–23 (1957)

    Google Scholar 

  • Weisburger,J.H., Russel,M.N., Ward,J.M., Viguera,C., Weisburger,E.K.: Modification of diethylnitrosamine liver-carcinogenesis with phenobarbital but not with immunosupression. J. nat. Cancer Inst. 54, 1185–1188 (1975)

    Google Scholar 

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Supported by visitors research grant of Deutsches Krebsforschungszentrum, Heidelberg, Germany and by Fonds de la Recherche Scientifique Médicale, Belgique

I wish to thank Professor P. Bannasch, Division of Cytopathology, Institute of Experimental Pathology, German Cancer Research Center, Heidelberg, Germany, for his friendly help and precious comments.

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Taper, H.S. Induction of the deficient acid DNAse activity in mouse interfollicular epidermis by croton oil as a possible tumor promoting mechanism. Z. Krebsforsch. 90, 197–210 (1977). https://doi.org/10.1007/BF00285326

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  • DOI: https://doi.org/10.1007/BF00285326

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