- Email: [email protected]
P02: Carcinogenicity and in vivo mutagenicity of 1,4-dioxane in gpt delta rats
ARTICLE IN PRESS 282
Abstracts / Experimental and Toxicologic Pathology 61 (2009) 257–295
Poster Abstracts
Spontaneous tumors of mammary gland are infrequent in male rats. A spontaneous adenocarcinoma of the mammary gland was observed in a 37-week-old male WNIN (Wistar/NIN) rat from the breeding colony of IIBAT. The rat had a subcutaneous mass at the left lateral aspect of neck measuring approximately 4 cm in diameter. In our literature search, we did not find any reports of spontaneous malignant neoplasms of the male mammary gland in this age group. The histological features of this neoplasm are similar to those described in female rats, with the exception of a lack of functional differentiation. Immunohistochemical staining of the tumor for smooth muscle actin and cytokeratin 14 was positive, which is consistent with a neoplasm of mammary origin.
a stabilizer for chlorinated solvent. However, little is known about the in vivo mutagenic effects of this rat liver carcinogen. The purpose of the present study is to investigate the dose-response relationship for in vivo mutagenicity and carcinogenicity of 1,4-dioxane in the livers of gpt delta transgenic rats, an animal model for in vivo mutagenicity analysis. Thirty, 6-week-old male gpt delta rats were divided into four groups and received 1,4-dioxane in drinking water at the concentrations of 0, 200, 1000, 5000 ppm up to 16 weeks, respectively. After the completion of treatment, all the rats were killed under ether anesthesia and livers were excised. Halves of the livers were fixed in 10% buffered formalin followed by paraffin embedding for histological analysis and the rests were frozen for molecular analysis. The number of glutathione S-transferase placental form (GST-P)-positive foci, a rat liver preneoplastic marker and PCNA-positive cell index, a marker for cell proliferation, were determined immunohistochemically, and mutation frequency followed by DNA sequencing was examined using frozen liver tissue. The number of GST-P-positive foci and PCNA-positive cell index were significantly (po0.0001, 0.01, respectively) increased only in the 5000 ppm group compared with control group. No difference was detected in all other groups. Mutation analysis revealed that treatment with 5000 ppm significantly (po0.001) increased the mutation frequencies of gpt transgene gene compared to control group, while doses up to 1000 ppm showed no effects. These results indicate the existence of threshold for liver carcinogenicity and in vivo mutagenicity of 1,4dioxane.
doi: 10.1016/j.etp.2009.02.038
doi: 10.1016/j.etp.2009.02.039
P02 Carcinogenicity and in vivo mutagenicity of 1,4-dioxane in gpt delta rats
P03 A novel marker, alpha2-macroglobulin and GRP78, characteristic of rat hepatocellular preneoplastic and neoplastic lesions undetectable by Glutathione S-transferase placental form
Neoplasia P01 Spontaneous mammary gland adenocarcinoma in a 37-week-old male Wistar rat P. Kalaiselvana, S. Vijayakumara, K. Hemalathaa, Yogeshkumar V. Murkundea, Ronald A. Herbertb, Monique Y. Wellsc a International Institute of Biotechnology And Toxicology (IIBAT), Padappai-601301, Kancheepuram district, Tamilnadu, India b Laboratory of Experimental Pathology, NIEHS, Research Triangle Park, NC, USA c CEHTRA, 43, rue Laroque, 33560 Sainte-Eulalie, France
Shoji Fukushimaa,b, Min Weib, Masako Omorib, Keiichirou Morimurab, Anna Kinoshitab, Kenichi Masumurac, Takehiko Nohmic, Hideki Wanibuchib a Japan Bioassay Research Center, Japan Industrial Safety and Health Association, Kanagawa 257-0015, Japan b Department of Pathology, Osaka city University Medical School, Osaka 545-8585, Japan c Division of Genetics and Mutagenesis, National Institute of Health Sciences, Tokyo 158 8501, Japan
Masahiko Kushidaa,b, Tokuo Sukataa, Satoshi Uwagawaa, Keisuke Ozakia, Keiichirou Morimurab, Hideki Wanibuchib, Shoji Fukushimac a Environmental and Health Science Laboratory, Sumitomo Chemical Co., Ltd., Japan b Department of Pathology, Osaka City University Medical School, Japan c Japan Bioassay Research Center, Japan
1,4-Dioxane is primarily used as industrial solvent for paints, surface-treating agent for artificial leather and is
Previously, we reported that alpha2-macroglobulin (alpha2M) was candidate for a novel marker characteristic
Abstracts / Experimental and Toxicologic Pathology 61 (2009) 257–295
Poster Abstracts
Spontaneous tumors of mammary gland are infrequent in male rats. A spontaneous adenocarcinoma of the mammary gland was observed in a 37-week-old male WNIN (Wistar/NIN) rat from the breeding colony of IIBAT. The rat had a subcutaneous mass at the left lateral aspect of neck measuring approximately 4 cm in diameter. In our literature search, we did not find any reports of spontaneous malignant neoplasms of the male mammary gland in this age group. The histological features of this neoplasm are similar to those described in female rats, with the exception of a lack of functional differentiation. Immunohistochemical staining of the tumor for smooth muscle actin and cytokeratin 14 was positive, which is consistent with a neoplasm of mammary origin.
a stabilizer for chlorinated solvent. However, little is known about the in vivo mutagenic effects of this rat liver carcinogen. The purpose of the present study is to investigate the dose-response relationship for in vivo mutagenicity and carcinogenicity of 1,4-dioxane in the livers of gpt delta transgenic rats, an animal model for in vivo mutagenicity analysis. Thirty, 6-week-old male gpt delta rats were divided into four groups and received 1,4-dioxane in drinking water at the concentrations of 0, 200, 1000, 5000 ppm up to 16 weeks, respectively. After the completion of treatment, all the rats were killed under ether anesthesia and livers were excised. Halves of the livers were fixed in 10% buffered formalin followed by paraffin embedding for histological analysis and the rests were frozen for molecular analysis. The number of glutathione S-transferase placental form (GST-P)-positive foci, a rat liver preneoplastic marker and PCNA-positive cell index, a marker for cell proliferation, were determined immunohistochemically, and mutation frequency followed by DNA sequencing was examined using frozen liver tissue. The number of GST-P-positive foci and PCNA-positive cell index were significantly (po0.0001, 0.01, respectively) increased only in the 5000 ppm group compared with control group. No difference was detected in all other groups. Mutation analysis revealed that treatment with 5000 ppm significantly (po0.001) increased the mutation frequencies of gpt transgene gene compared to control group, while doses up to 1000 ppm showed no effects. These results indicate the existence of threshold for liver carcinogenicity and in vivo mutagenicity of 1,4dioxane.
doi: 10.1016/j.etp.2009.02.038
doi: 10.1016/j.etp.2009.02.039
P02 Carcinogenicity and in vivo mutagenicity of 1,4-dioxane in gpt delta rats
P03 A novel marker, alpha2-macroglobulin and GRP78, characteristic of rat hepatocellular preneoplastic and neoplastic lesions undetectable by Glutathione S-transferase placental form
Neoplasia P01 Spontaneous mammary gland adenocarcinoma in a 37-week-old male Wistar rat P. Kalaiselvana, S. Vijayakumara, K. Hemalathaa, Yogeshkumar V. Murkundea, Ronald A. Herbertb, Monique Y. Wellsc a International Institute of Biotechnology And Toxicology (IIBAT), Padappai-601301, Kancheepuram district, Tamilnadu, India b Laboratory of Experimental Pathology, NIEHS, Research Triangle Park, NC, USA c CEHTRA, 43, rue Laroque, 33560 Sainte-Eulalie, France
Shoji Fukushimaa,b, Min Weib, Masako Omorib, Keiichirou Morimurab, Anna Kinoshitab, Kenichi Masumurac, Takehiko Nohmic, Hideki Wanibuchib a Japan Bioassay Research Center, Japan Industrial Safety and Health Association, Kanagawa 257-0015, Japan b Department of Pathology, Osaka city University Medical School, Osaka 545-8585, Japan c Division of Genetics and Mutagenesis, National Institute of Health Sciences, Tokyo 158 8501, Japan
Masahiko Kushidaa,b, Tokuo Sukataa, Satoshi Uwagawaa, Keisuke Ozakia, Keiichirou Morimurab, Hideki Wanibuchib, Shoji Fukushimac a Environmental and Health Science Laboratory, Sumitomo Chemical Co., Ltd., Japan b Department of Pathology, Osaka City University Medical School, Japan c Japan Bioassay Research Center, Japan
1,4-Dioxane is primarily used as industrial solvent for paints, surface-treating agent for artificial leather and is
Previously, we reported that alpha2-macroglobulin (alpha2M) was candidate for a novel marker characteristic