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DNA damage in mammalian tissues II. Damages in different tissues of mouse after administration of N-ethyl-N-nitrosourea
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hemoglobin and cytochrome c, also showed strong inhibitory effects on these activated mutagens. Bovine serum albumin, used as a control for the globular proteins, did not affect the mutagenicity. These results suggest direct interactions between the heme nucleus and these mutagens. The nature of this interaction is being investigated.
3 Furihata, C., and J.A. Heddle 1, Department of Molecular Oncology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108 (Japan), and ~ Ludwig Institute for Cancer Research, Toronto Branch, Toronto, Ont. M4Y 1M4 (Canada) Induction of nuclear aberrations in vivo in rat gut epithelium by l-methyl-l-nitrosourea A 1-methyl-l-nitrosourea (MNU) solution was administered to groups of 5 male F344 rats (7 weeks old) by gastric tube. Their gut was removed, fixed in 10% neutralized formalin and embedded in paraffin. Histological sections (5/~m thick) were stained with Feulgen and counter-stained with fast green. Nuclear aberrations (NA) were scored along 10 longitudinal crypt columns or 200 cells per rat. Administration of MNU (100 m g / k g body weight) induced maximal NA in the esophagus, forestomach epidermis and fundic mucosa after 48 h (10.0 _+ 4.1, 18.2 _+ 5.3 and 3.4 +_ 2.3/200 cells respectively). Values of 5.2 + 3.2, 11.4 _+ 3.9 and 4.0 + 3.1/crypt were observed in the pyloric mucosa at 6 h, duodenal mucosa at 3 h and colon mucosa at 6 h, respectively. Using 34 to 135 mg M N U / k g body weight, a dose response was observed with a maximum at 100 mg/kg.
4 Furukawa, H., and K. Kawai, Laboratory of Environmental Science, Faculty of Pha;'maceutical Sciences, Meijo University, Nagoya (Japan) Mutagenicity-structure relationship of dinitrobenzene derivatives
7 dinitrobenzene derivatives were examined for their mutagenicity in the Ames test. In the assay using S. typhimurium TA98, with or without metabolic activation, m-dinitrobenzene was the most active of the 3 positional isomers and 1-substituted 2,4-dinitrobenzenes. In the assay with S. typhimurium TA100 with metabolic activation, mdinitrobenzene was again the most active. With TA100 without metabolic activation, however, 1chloro-2,4-dinitrobenzene was the most active.
5 Hachiya, N., and Y. Takizawa, Department of Public Health, Akita University School of Medicine, Akita 010 (Japan) DNA damage in mammalian tissues 1I. Damages in different tissues of mouse after administration of N-ethyi-N-nitrosourea DNA damage and repair in mouse tissues caused by intraperitoneal administration of 25-200 m g / k g N-ethyl-N-nitrosourea (ENU) were investigated. The assay used was alkaline elution through a membrane filter and the DNA was eluted using tetra-n-propylammonium hydroxide. A crude nuclei fraction of the liver, a homogenate of the brain or the testis, and a flush-out suspension of the bone marrow were examined. The elution pattern showed that DNA-strand breaks were induced in a dose-dependent manner in all the tissues examined. Elution rate constants, which were calculated from the linear portions of the elution profiles, were analyzed at different times following ENU treatment. The results showed that DNA-strand breaks in the liver cells reached a maximum between 2 and 4 h after the injection and subsequent recovery was relatively slow leaving substantial damage at 24 h. In the brain and the bone marrow, the extent of the lesion produced by ENU was not less than that of the liver. However, they were repaired more rapidly than in the liver. The maximum damage induced in the testis was significantly smaller than the lesion in the other tissues.
hemoglobin and cytochrome c, also showed strong inhibitory effects on these activated mutagens. Bovine serum albumin, used as a control for the globular proteins, did not affect the mutagenicity. These results suggest direct interactions between the heme nucleus and these mutagens. The nature of this interaction is being investigated.
3 Furihata, C., and J.A. Heddle 1, Department of Molecular Oncology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108 (Japan), and ~ Ludwig Institute for Cancer Research, Toronto Branch, Toronto, Ont. M4Y 1M4 (Canada) Induction of nuclear aberrations in vivo in rat gut epithelium by l-methyl-l-nitrosourea A 1-methyl-l-nitrosourea (MNU) solution was administered to groups of 5 male F344 rats (7 weeks old) by gastric tube. Their gut was removed, fixed in 10% neutralized formalin and embedded in paraffin. Histological sections (5/~m thick) were stained with Feulgen and counter-stained with fast green. Nuclear aberrations (NA) were scored along 10 longitudinal crypt columns or 200 cells per rat. Administration of MNU (100 m g / k g body weight) induced maximal NA in the esophagus, forestomach epidermis and fundic mucosa after 48 h (10.0 _+ 4.1, 18.2 _+ 5.3 and 3.4 +_ 2.3/200 cells respectively). Values of 5.2 + 3.2, 11.4 _+ 3.9 and 4.0 + 3.1/crypt were observed in the pyloric mucosa at 6 h, duodenal mucosa at 3 h and colon mucosa at 6 h, respectively. Using 34 to 135 mg M N U / k g body weight, a dose response was observed with a maximum at 100 mg/kg.
4 Furukawa, H., and K. Kawai, Laboratory of Environmental Science, Faculty of Pha;'maceutical Sciences, Meijo University, Nagoya (Japan) Mutagenicity-structure relationship of dinitrobenzene derivatives
7 dinitrobenzene derivatives were examined for their mutagenicity in the Ames test. In the assay using S. typhimurium TA98, with or without metabolic activation, m-dinitrobenzene was the most active of the 3 positional isomers and 1-substituted 2,4-dinitrobenzenes. In the assay with S. typhimurium TA100 with metabolic activation, mdinitrobenzene was again the most active. With TA100 without metabolic activation, however, 1chloro-2,4-dinitrobenzene was the most active.
5 Hachiya, N., and Y. Takizawa, Department of Public Health, Akita University School of Medicine, Akita 010 (Japan) DNA damage in mammalian tissues 1I. Damages in different tissues of mouse after administration of N-ethyi-N-nitrosourea DNA damage and repair in mouse tissues caused by intraperitoneal administration of 25-200 m g / k g N-ethyl-N-nitrosourea (ENU) were investigated. The assay used was alkaline elution through a membrane filter and the DNA was eluted using tetra-n-propylammonium hydroxide. A crude nuclei fraction of the liver, a homogenate of the brain or the testis, and a flush-out suspension of the bone marrow were examined. The elution pattern showed that DNA-strand breaks were induced in a dose-dependent manner in all the tissues examined. Elution rate constants, which were calculated from the linear portions of the elution profiles, were analyzed at different times following ENU treatment. The results showed that DNA-strand breaks in the liver cells reached a maximum between 2 and 4 h after the injection and subsequent recovery was relatively slow leaving substantial damage at 24 h. In the brain and the bone marrow, the extent of the lesion produced by ENU was not less than that of the liver. However, they were repaired more rapidly than in the liver. The maximum damage induced in the testis was significantly smaller than the lesion in the other tissues.