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Toxicologic Pathology
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*N-NITROSO-N-METHYLUREA
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Journal Article

Retinal Degeneration Induced by N-Methyl-N-Nitrosourea and Detection of 7-Methyldeoxyguanosine in the Rat Retina

Hiroshi Ogino

Second Department of Pathology

Mitsuya Ito

Second Department of Pathology

Kazuyuki Matsumoto

Second Department of Pathology

Sigeru Yagyu

Laboratory Animal Center, Fujita Health University School of Medicine, Toyoake, Aichi 470–11, Japan

Hiroyuki Tsuda

Second Department of Pathology

Iwao Hirono

Second Department of Pathology

Christopher P. Wild

Unit of Mechanisms of Carcinogenesis, International Agency for Research on Cancer, 150 cours Albert Thomas, 69372 Lyon Cedex, 08 France

Ruggero Montesano

Unit of Mechanisms of Carcinogenesis, International Agency for Research on Cancer, 150 cours Albert Thomas, 69372 Lyon Cedex, 08 France

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.

Key Words: Alkylation • rabbit • photoreceptor layer • outer nuclear layer

Toxicologic Pathology, Vol. 21, No. 1, 21-25 (1993)
DOI: 10.1177/019262339302100103


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