The Experts below are selected from a list of 51 Experts worldwide ranked by ideXlab platform
Takashi Sugimura - One of the best experts on this subject based on the ideXlab platform.
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rat p53 gene mutations in primary Zymbal Gland tumors induced by 2 amino 3 methylimidazo 4 5 f quinoline a food mutagen
Proceedings of the National Academy of Sciences of the United States of America, 1992Co-Authors: Hiroshi Makino, Takashi Sugimura, Yukihito Ishizaka, Atsumi Tsujimoto, Takuro Nakamura, Masahiko Onda, Minako NagaoAbstract:There are reports of p53 gene mutations in various human cancers but not in rat tumor cell lines or rat primary tumor tissue. We found a p53 gene mutation in a cell line of a spontaneous squamous cell carcinoma of the rat Zymbal Gland, SCC131, at codon 171 by direct sequencing of cDNA fragments amplified by PCR. We tested for p53 gene mutations in 15 primary Zymbal Gland tumors induced by 2-amino-3-methylimidazo[4,5-f]quinoline by single-strand conformation polymorphism analysis of the PCR-amplified cDNA products. Samples of four tumors showed mobility shifts. Direct sequencing revealed that all these tumors had mutations in conserved regions or in scattered conserved residues. Single-strand conformation polymorphism analysis of cDNA suggested that mRNA from the wild-type allele of the p53 gene was not present in tumor cells of three of four positive cases, although genomic DNA analysis indicated that the wild-type allele was retained in all the cases. All mutations were found at a guanine base: three mutations were guanine----pyrimidine transversions and one was a deletion of a guanine base within a G+C-rich sequence. These findings indicate that 2-amino-3-methylimidazo[4,5-f]quinoline may be directly involved in induction of these mutations by forming DNA adducts at various sites in the p53 gene.
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Carcinogenicities of heterocyclic amines in cooked food
Mutation research, 1991Co-Authors: Hiroko Ohgaki, Shozo Takayama, Takashi SugimuraAbstract:Mutagenic heterocyclic amines in cooked foods were carcinogenic to mice, rats and/or monkeys, when they were given orally continuously. The most common target organ was the liver, but in CDF1 mice lung tumors, forestomach tumors, lymphomas/leukemias, and blood vessel tumors in the brown adipose tissues were also induced. In F344 rats, in addition to liver tumors, tumors in the Zymbal Gland, skin, clitoral Gland, small and large intestines, oral cavity, and mammary Gland were also induced. Monkeys given IQ developed metastatic hepatocellular carcinomas.
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mutational activation of c ha ras gene in squamous cell carcinomas of rat Zymbal Gland induced by carcinogenic heterocyclic amines
Molecular Carcinogenesis, 1991Co-Authors: Mami Kudo, Tsutomu Ogura, Hiroyasu Esumi, Takashi SugimuraAbstract:The activation of the c-Ha-ras gene and its carcinogen specificity were examined in squamous cell carcinomas (SCCs) induced by the mutagenic heterocyclic amines 2-amino-3-methylimidazo [4,5-f]quinoline (IQ),2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), and 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ) in the Zymbal Gland in rats. DNA fragments of the c-Ha-ras gene were amplified from formalin-fixed and paraffin-embedded tissues by polymerase chain reaction and analyzed for activating mutations involving codons 12, 13, and 61 by oligonucleotide differential hybridization and sequencing. c-Ha-ras mutations were found in four of seven and two of six Zymbal Gland SCCs induced by IQ and MeIQx, respectively. These mutations were located in either codon 13 or 61. In the case of MeIQ, point mutations at the second nucleotide of codon 13 were found in nine of the total 14 Zymbal Gland SCCs and in one papilloma. Of the nine SCCs that had mutations in codon 13, two possessed mutations at the second nucleotide of codon 12 as well. Most reported mutations in c-Ha-ras are located at codon 12 or 61, but the heterocyclic amines in this study induced mutations not only at codons 12 and 61 but also in codon 13. Transversions were the dominant mutation induced by these heterocyclic amines.
Minako Nagao - One of the best experts on this subject based on the ideXlab platform.
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rat p53 gene mutations in primary Zymbal Gland tumors induced by 2 amino 3 methylimidazo 4 5 f quinoline a food mutagen
Proceedings of the National Academy of Sciences of the United States of America, 1992Co-Authors: Hiroshi Makino, Takashi Sugimura, Yukihito Ishizaka, Atsumi Tsujimoto, Takuro Nakamura, Masahiko Onda, Minako NagaoAbstract:There are reports of p53 gene mutations in various human cancers but not in rat tumor cell lines or rat primary tumor tissue. We found a p53 gene mutation in a cell line of a spontaneous squamous cell carcinoma of the rat Zymbal Gland, SCC131, at codon 171 by direct sequencing of cDNA fragments amplified by PCR. We tested for p53 gene mutations in 15 primary Zymbal Gland tumors induced by 2-amino-3-methylimidazo[4,5-f]quinoline by single-strand conformation polymorphism analysis of the PCR-amplified cDNA products. Samples of four tumors showed mobility shifts. Direct sequencing revealed that all these tumors had mutations in conserved regions or in scattered conserved residues. Single-strand conformation polymorphism analysis of cDNA suggested that mRNA from the wild-type allele of the p53 gene was not present in tumor cells of three of four positive cases, although genomic DNA analysis indicated that the wild-type allele was retained in all the cases. All mutations were found at a guanine base: three mutations were guanine----pyrimidine transversions and one was a deletion of a guanine base within a G+C-rich sequence. These findings indicate that 2-amino-3-methylimidazo[4,5-f]quinoline may be directly involved in induction of these mutations by forming DNA adducts at various sites in the p53 gene.
Shoji Fukushima - One of the best experts on this subject based on the ideXlab platform.
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two year inhalation study of carcinogenicity and chronic toxicity of 1 4 dioxane in male rats
Inhalation Toxicology, 2009Co-Authors: Tatsuya Kasai, Hirokazu Kano, Yumi Umeda, Toshiaki Sasaki, Naoki Ikawa, Tomoshi Nishizawa, Kasuke Nagano, Heihachiro Arito, Hiroshi Nagashima, Shoji FukushimaAbstract:Carcinogenicity and chronic toxicity of 1,4-dioxane were examined by inhalation exposure of 50 male F344 rats to 1,4-dioxane vapor at 0 (clean air), 50, 250, or 1250 ppm (v/v) for 6 h/day, 5 days/wk, and 104 wk. Survival rates of 250 and 1250 ppm-exposed groups were decreased near the end of the 2-yr exposure period, due probably to the occurrence of malignant tumors. A statistically significant but marginal decrement of terminal body weight (<10%) was found in the 1250 ppm-exposed group, suggesting slight systemic toxicity. Significant changes in plasma levels of AST, ALT, ALP, and γ-GTP and relative weight of the liver occurred in the 1250 ppm-exposed group. Dose-dependent and statistically significant increases in incidences of nasal squamous cell carcinomas, hepatocellular adenomas, and peritoneal mesotheliomas were found primarily in the 1250 ppm-exposed group. The incidences of renal cell carcinomas, fibroadenomas in the mammary Gland, and adenomas in the Zymbal Gland were also increased dose-depend...
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two year inhalation study of carcinogenicity and chronic toxicity of 1 4 dioxane in male rats
Inhalation Toxicology, 2009Co-Authors: Tatsuya Kasai, Hirokazu Kano, Yumi Umeda, Toshiaki Sasaki, Naoki Ikawa, Tomoshi Nishizawa, Kasuke Nagano, Heihachiro Arito, Hiroshi Nagashima, Shoji FukushimaAbstract:Carcinogenicity and chronic toxicity of 1,4-dioxane were examined by inhalation exposure of 50 male F344 rats to 1,4-dioxane vapor at 0 (clean air), 50, 250, or 1250 ppm (v/v) for 6 h/day, 5 days/wk, and 104 wk. Survival rates of 250 and 1250 ppm-exposed groups were decreased near the end of the 2-yr exposure period, due probably to the occurrence of malignant tumors. A statistically significant but marginal decrement of terminal body weight (<10%) was found in the 1250 ppm-exposed group, suggesting slight systemic toxicity. Significant changes in plasma levels of AST, ALT, ALP, and gamma-GTP and relative weight of the liver occurred in the 1250 ppm-exposed group. Dose-dependent and statistically significant increases in incidences of nasal squamous cell carcinomas, hepatocellular adenomas, and peritoneal mesotheliomas were found primarily in the 1250 ppm-exposed group. The incidences of renal cell carcinomas, fibroadenomas in the mammary Gland, and adenomas in the Zymbal Gland were also increased dose-dependently. Preneoplastic lesions occurred in the nasal cavity and liver of the 1,4-dioxane-exposed groups. As nonneoplastic lesions, the significantly increased incidences of nuclear enlargement, atrophy, and respiratory metaplasia in the nasal cavity were noted at 50 ppm and above. A LOAEL (lowest observed adverse effect level) was determined at 50 ppm for the nasal endpoint of general chronic toxicity. This study provides clear evidence of carcinogenicity for 1,4-dioxane in male rats. A cytotoxic-proliferative and in vivo genotoxic mode of action is suggested to operate in 1,4-dioxane-induced carcinogenesis.
Hiroshi Makino - One of the best experts on this subject based on the ideXlab platform.
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rat p53 gene mutations in primary Zymbal Gland tumors induced by 2 amino 3 methylimidazo 4 5 f quinoline a food mutagen
Proceedings of the National Academy of Sciences of the United States of America, 1992Co-Authors: Hiroshi Makino, Takashi Sugimura, Yukihito Ishizaka, Atsumi Tsujimoto, Takuro Nakamura, Masahiko Onda, Minako NagaoAbstract:There are reports of p53 gene mutations in various human cancers but not in rat tumor cell lines or rat primary tumor tissue. We found a p53 gene mutation in a cell line of a spontaneous squamous cell carcinoma of the rat Zymbal Gland, SCC131, at codon 171 by direct sequencing of cDNA fragments amplified by PCR. We tested for p53 gene mutations in 15 primary Zymbal Gland tumors induced by 2-amino-3-methylimidazo[4,5-f]quinoline by single-strand conformation polymorphism analysis of the PCR-amplified cDNA products. Samples of four tumors showed mobility shifts. Direct sequencing revealed that all these tumors had mutations in conserved regions or in scattered conserved residues. Single-strand conformation polymorphism analysis of cDNA suggested that mRNA from the wild-type allele of the p53 gene was not present in tumor cells of three of four positive cases, although genomic DNA analysis indicated that the wild-type allele was retained in all the cases. All mutations were found at a guanine base: three mutations were guanine----pyrimidine transversions and one was a deletion of a guanine base within a G+C-rich sequence. These findings indicate that 2-amino-3-methylimidazo[4,5-f]quinoline may be directly involved in induction of these mutations by forming DNA adducts at various sites in the p53 gene.
Tatsuya Kasai - One of the best experts on this subject based on the ideXlab platform.
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two year inhalation study of carcinogenicity and chronic toxicity of 1 4 dioxane in male rats
Inhalation Toxicology, 2009Co-Authors: Tatsuya Kasai, Hirokazu Kano, Yumi Umeda, Toshiaki Sasaki, Naoki Ikawa, Tomoshi Nishizawa, Kasuke Nagano, Heihachiro Arito, Hiroshi Nagashima, Shoji FukushimaAbstract:Carcinogenicity and chronic toxicity of 1,4-dioxane were examined by inhalation exposure of 50 male F344 rats to 1,4-dioxane vapor at 0 (clean air), 50, 250, or 1250 ppm (v/v) for 6 h/day, 5 days/wk, and 104 wk. Survival rates of 250 and 1250 ppm-exposed groups were decreased near the end of the 2-yr exposure period, due probably to the occurrence of malignant tumors. A statistically significant but marginal decrement of terminal body weight (<10%) was found in the 1250 ppm-exposed group, suggesting slight systemic toxicity. Significant changes in plasma levels of AST, ALT, ALP, and γ-GTP and relative weight of the liver occurred in the 1250 ppm-exposed group. Dose-dependent and statistically significant increases in incidences of nasal squamous cell carcinomas, hepatocellular adenomas, and peritoneal mesotheliomas were found primarily in the 1250 ppm-exposed group. The incidences of renal cell carcinomas, fibroadenomas in the mammary Gland, and adenomas in the Zymbal Gland were also increased dose-depend...
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two year inhalation study of carcinogenicity and chronic toxicity of 1 4 dioxane in male rats
Inhalation Toxicology, 2009Co-Authors: Tatsuya Kasai, Hirokazu Kano, Yumi Umeda, Toshiaki Sasaki, Naoki Ikawa, Tomoshi Nishizawa, Kasuke Nagano, Heihachiro Arito, Hiroshi Nagashima, Shoji FukushimaAbstract:Carcinogenicity and chronic toxicity of 1,4-dioxane were examined by inhalation exposure of 50 male F344 rats to 1,4-dioxane vapor at 0 (clean air), 50, 250, or 1250 ppm (v/v) for 6 h/day, 5 days/wk, and 104 wk. Survival rates of 250 and 1250 ppm-exposed groups were decreased near the end of the 2-yr exposure period, due probably to the occurrence of malignant tumors. A statistically significant but marginal decrement of terminal body weight (<10%) was found in the 1250 ppm-exposed group, suggesting slight systemic toxicity. Significant changes in plasma levels of AST, ALT, ALP, and gamma-GTP and relative weight of the liver occurred in the 1250 ppm-exposed group. Dose-dependent and statistically significant increases in incidences of nasal squamous cell carcinomas, hepatocellular adenomas, and peritoneal mesotheliomas were found primarily in the 1250 ppm-exposed group. The incidences of renal cell carcinomas, fibroadenomas in the mammary Gland, and adenomas in the Zymbal Gland were also increased dose-dependently. Preneoplastic lesions occurred in the nasal cavity and liver of the 1,4-dioxane-exposed groups. As nonneoplastic lesions, the significantly increased incidences of nuclear enlargement, atrophy, and respiratory metaplasia in the nasal cavity were noted at 50 ppm and above. A LOAEL (lowest observed adverse effect level) was determined at 50 ppm for the nasal endpoint of general chronic toxicity. This study provides clear evidence of carcinogenicity for 1,4-dioxane in male rats. A cytotoxic-proliferative and in vivo genotoxic mode of action is suggested to operate in 1,4-dioxane-induced carcinogenesis.
