RETINAL DEGENERATION INDUCED BY N-METHYL-N-NITROSOUREA AND DETECTION OF 7-METHYLDEOXYGUANOSINE IN THE RAT RETINA

被引：35

作者：

OGINO, H ^{[1
]}

ITO, M ^{[1
]}

MATSUMOTO, K ^{[1
]}

YAGYU, S ^{[1
]}

TSUDA, H ^{[1
]}

HIRONO, I ^{[1
]}

WILD, CP ^{[1
]}

MONTESANO, R ^{[1
]}

机构：

[1] FUJITA HLTH UNIV,SCH MED,DEPT PATHOL,TOYOAKE,AICHI 47011,JAPAN

来源：

TOXICOLOGIC PATHOLOGY | 1993年 / 21卷 / 01期

关键词：

ALKYLATION; RABBIT; PHOTORECEPTOR LAYER; OUTER NUCLEAR LAYER;

D O I：

10.1177/019262339302100103

中图分类号：

R36 [病理学];

学科分类号：

100104 ;

摘要：

Retinal degeneration induced by a single parenteral dose (40 mg) of N-methyl-N-nitrosourea (MNU) was studied in rats and rabbits. Sequential observations showed that severe pathological changes, that is, complete or widespread destruction of the photoreceptor layer and the outer nuclear layer of the retina, occurred in both animals by 72 hr after the administration of MNU. At week 5, at the end stage of the retinal degeneration induced by MNU, thin remnants remained with the inner nuclear layer in direct contact with the pigment epithelium. An additional immunohistochemistry study using antibodies against 7-methyldeoxyguanosine (7-mdGua), revealed the presence of high levels of 7-mdGua DNA adducts in the nuclei of the outer nuclear layer cells. This finding suggests that the alkylation of the outer nuclear layer by MNU was the direct cause of the retinal degeneration seen in these animals.

引用

页码：21 / 25

页数：5

共 11 条

[1] Abbott P.J., Saffhill R., DNA synthesis with methylated poly(dC-dG) templates. Evidence for a competitive nature to miscoding by O6-methylguaî nine, Biochim. Biophys. Acta, 562, pp. 51-61, (1979)
[2] Asamoto M., Mikheev A.M., Jidug Y.Z., Wild C.P., Hall J., Montesano R., Immunohistochemical detection of DNA alkylation adducts in rat and hamster liver after treatment with dimethylnitrosamine, Exp. Pathol, 41, pp. 71-78, (1991)
[3] Degan P., Montesano R., Wild C.P., Antibodies against 7-methyldeoxyguanosine: Its detection in rat peripheral blood lymphocyte DNA and potential applications to molecular epidemiology, Cancer Res, 48, pp. 5065-5070, (1988)
[4] Herrold K.M., Pigmentary degeneration of the retina induced by N-methyl-N-nitrosourea, Arch. Ophthal, 78, pp. 650-653, (1976)
[5] Heywood R., Gopinath C., Morphological assessment of visual dysfunction, Toxicol. Pathol, 18, pp. 204-217, (1990)
[6] N-nitroso-N-methylurea. IARC monographs on the evaluation of the carcinogenic risk of chemicals to humans, Some N-nitroso Compounds, 17, pp. 227-255, (1978)
[7] Ishikawa T., Sakurai J., Retinal injury induced by N-methyl-N-nitrosourea (MNU), Trans. Societatis Patholog. Jappon, LXXIV, (1985)
[8] Ludlum D.B., The properties of 7-methylgua-nine-containing templates for ribonucleic acid polymerase, J. Biol. Chem, 245, pp. 477-482, (1970)
[9] Meier-Ruge R., Drug induced retinopathy, CRC Crit. Rev. Toxicol, 1, pp. 325-360, (1972)
[10] Saffhill R., Margison G.P., O'Connor P.J., Mechanisms of carcinogenesis induced by alkylating agents, Biochim. Biophys. Acta, 82, pp. 111-145, (1985)

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