Summary
Carcinomas of the glandular stomach were induced in 82 Wistar rats by means of MNNG1. Part of the group also received high doses of Vitamin A. A consistently significant increase in depth of invasion, i. e. progression of the pathological tumor stage, was observed under the influence of Vitamin A. The frequency of tumor occurrence was not significantly altered. The labilizing effect of Vitamin A on cellular membrane systems is the probable mechanism of Vitamin A's tumor-promoting influence in our experiment: 1. By way of destruction of lysosomal membranes, enzymes, cancerogens, and viruses would be released, leading directly or indirectly to an alteration of the DNA. 2. Damage of cell membranes would lead to loss of the contact inhibition.
Zusammenfassung
In einer Untersuchung an 82 Wistar-Ratten wurden Carcinome des Drüsenmagens mit MNNG erzeugt. Ein Teil der Tiere erhielt zusätzlich hohe Dosen Vitamin A. Wir sahen eine statistisch signifikante Zunahme der Invasionstiefe und damit der Progression des Tumorstadiums unter Vitamin A-Einfluß. Die Häufigkeit des Auftretens von Tumoren war hingegen nicht signifikant verändert. Als Ursache des tumorfördernden Einflußes von Vitamin A in unserem Experiment ist vor allem sein labilisierender Effekt auf celluläre Membransysteme zu diskutieren: 1. Durch Zerstörung lysosomaler Membranen werden Enzyme, Cancerogene und Viren freigesetzt, die direkt oder indirekt zu einer Alteration der DNA führen. 2. Durch Schädigung der Zellmembranen geht die Kontaktinhibition verloren.
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Literatur
Allison A (1973) Lysosomes in cancer. In: Dingle JT, Fell HB (eds) Lysosomes in biology and pathology, Vol 2. Elsevier, Amsterdam
Bollag W (1971) Vitamin A-Saure in der Tumortherapie. Schweiz Med Wochenschr 101: 11–17
Boren HG, Pauley J, Wright EC, Kaufman DG, Smith JM, Harris CC (1974) Cell populations in the hamster tracheal epithelium in relation to vitamin-A-status. Int J Vit Nutr Res 44:382–390
Brown IV, Lane BP, Pearson J (1977) Effects of depot injections of retinyl palmitate on 7, 12-dimethylbenzanthracene-induced preneoplastic changes in rat skin. J Natl Cancer Inst 58: 1347–1355
Carr AJ (1963) Effect of some glycosidase-inhibitors on experimental tumors in the mouse. Nature 198:1104
Chopra DP, Wilkoff LJ (1977) Reversal by vitamin A-analogues (retinoids) of hyperplasia induced by MNNG in mouse prostate organ cultures. J Natl Cancer Inst 58:923–930
Chu EW, Malmgren RA (1965) An inhibitory effect of vitamin A on the induction of tumors of the forestomach and cervix in the syrian hamsters by carcinogenic polycyclic hydrocarbons. Cancer Res 25:884–895
Dahm K Werner B (1976) Susceptibility of the resected stomach to experimental carcinogenesis. Z Krebsforsch 85:219–229
Doll R (1967) Worlwide distribution of gastrointestinal cancer. Natl Cancer Inst Monogr 25:173
Dresser DW (1968) Adjuvancity of vitamin A. Nature (Lond) 217:527
Felix EL, Loyd B, Cohen MH (1975) Inhibition of the growth and development of a transplantable murine melanoma by vitamin A. Science 189:886–887
Fukushima S, Hananouchi M, Shirai T (1976) Effect of plastic bead on gastric carcinogenesis in rat glandular and forestomach. Gann 67:197–205
Fukushima S, Hibino T, Shibata M, Tsuda H, Shirai T, Takahashi M, Ito N (1977) Effect of iodacetamide or tween 60 on methylnitrosocyanamide carcinogenesis in rat glandular and forestomach. Gann 68:813–818
Fukushima S, Tatematsu M, Takahashi M (1974) Combined effect of various surfactants on gastric carcinogenesis in rats. Gann 65:371–376
Higginson J (1967) Etiology of gastrointestinal causer in man. J Natl Cancer Inst Monogr 25:191
Hill DL, Shih TW (1974) Vitamin A-compounds and analogues as inhibitors of mixed-function oxidases that metabolize carcinogenic polycyclic hydrocarbons and other compounds. Cancer Res 34:564–570
Hirose F, Watanabe H, Takeichi N, Naito Y, Inoue S (1976) Effect of experimental immune atropic gastritis on the induction of gastric carcinoma by X-irradiation in ICR-mice. Gann 67:355–364
Kobori O, Gedigk P, Totovic V (1976) Early changes of glandular stomach in Wistar-rats ingesting MNNG: with special reference to light-microscopic, electron-microscopic and enzyme-histochemical study of the regeneration epithelium induced by MNNG. Z Krebsforsch 87:127–138
Levij IS, Polliak A (1968) Potentiating effect of vitamin A on DMBA-carcinogenesis in the hamster cheekpouch. Cancer 22:300–306
Levij IS, Rwomushana IW (1969) Enhancement of chemical carcinogenesis in the hamster cheekpouch by prior topical application of vitamin A palmitate. J Invest Dermatol 53:228–231
Matsukura N, Kawachi I, Sasajima K, Sano T (1979) Induction of intestinal metaplasia in the stomach of rats by MNNG. J Natl Cancer Inst 67:141–144
Moon RC, Grubbs CJ (1971) Retinylacetate inhibits mammary carcinogenesis induced by NMU. Nature 267:620–621
Narisawa T, Reddy BS (1976) Effect of vitamin A deficiency on rat colon carcinogenesis by MNNG. Cancer Res 36:1379–1383
Newberne PM, Rogers AE (1973) Rat colon carcinogenesis associated wit aflatoxin and marginal vitamin A. J Natl Cancer Inst 50:439–448
Poste G (1971) Sub-lethal autolysis: Modification of call periphery by lysosomal enzymes. Exp Cell Res 67:11–16
Roels OA (1973) The influence of vitamin A and E on lysosomes. In: Dingle JT (ed) Lysosomes, Vol 1. Elsevier, Amsterdam, p 254
Rogers AE, Herndon BJ, Newberne PM (1978) Induction by DMH of intestinal carcinoma in normal rats by BBN and DMH. Arzneimittelforschung 28:49–51
Seifter E, Rettura G, Padawer J (1976) Antipyretic and antiviral action of vitamin A in moloney sarcoma virus and poxvirus inoculated mice. J Natl Cancer Inst 57:355–359
Squire RA, Sporn MB (1977) Histopathological evaluation of the inhibitor of rat bladder carcinogenesis by 13-cis-RA. Cancer Res 37:2930–2936
Sugimura T, Fujimura S (1967) Tumor production in glandular stomach or rat by MNNG. Nature 216:943–944
Tabuchi Y, Ogino T (1974) Possible role of mucosal damage in stomach carcinogenesis wit MNNG in the rat. J Natl Cancer Inst 52:1589–1594
Tahara E, Haizuka S (1975) Effect of gastro-entero-pancreatic endocrine hormones on the histogenesis of gastric cancer in rats induced by MNNG; with special reference to development of scirrhous gastric cancer. Gann 66:421–426
Takahashi M, Shirai T (1976) Effect of fundic ulcers induced by iodoacetamide on development of gastric tumors in rats treated with MNNG. Gann 67:47–57
Tatsuta M, Itch T (1977) Effect of prolonged administration of gastrin on experimental carcinogenesis in rat stomach incuced by MNNG. Cancer Res 37:1808–1010
Tatematsu M, Takahashi M, Fukushima S, (1975) Effects in rats of sodium chloride on experimental gastric cancer induced by MNNG or Nitroquinoline-1-oxide. J Natl Cancer Inst 55:101–106
Uchida Y, Schlake W, Roessner A (1977) Development of tumors in the glandular stomach of rats after oral administration of carcinogens. I) Histological findings 199–212. II) Different cell types in antral carcinoma as revealed by electron microscopy 213–228. Z Krebsforsch 89
Ward JM, Sporn MB (1978) Dose response to intrarectal administration of NMU and histopathologic evaluation of the effect of two retinoids on colon lesions induced in rats. J Natl Cancer Inst 60:1489–1493
Weiss L (1969) Some effects of hypervitaminosis A on metastasis of spontaneous breast-cancer in mice. J Natl Cancer Inst 43:1045–1054
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MNNG = N-Methyl, N-Nitro, N-Nitroso-Guanidin
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Reimann, B., Mitschke, H. & Schreiber, H.W. Einfluß des Vitamin A auf die MNNG-induziert Cancerogenese im Drüsenmagen der Ratte. Langenbecks Arch Chiv 359, 65–73 (1983). https://doi.org/10.1007/BF01254150
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DOI: https://doi.org/10.1007/BF01254150