Short-term carcinogenicity study of N-methyl-N-nitrosourea in FVB-Trp53 heterozygous mice.
Carcinogenicity tests predict the tumorigenic potential of various substances in the human body by studying tumor induction in experimental animals. There is a need for studies that explore the use of FVB/N-Trp53em2Hwl/Korl (FVB-Trp53+/-) mice, created by TALEN-mediated gene targeting in Korea, in c...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2023-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0280214 |
| _version_ | 1797866059301126144 |
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| author | Na-Won Kim Sun-Min Seo Eun-Seon Yoo Ah-Reum Kang Ji-Hun Lee Jae-Hoon Lee Byeong-Cheol Kang Han-Woong Lee Yang-Kyu Choi |
| author_facet | Na-Won Kim Sun-Min Seo Eun-Seon Yoo Ah-Reum Kang Ji-Hun Lee Jae-Hoon Lee Byeong-Cheol Kang Han-Woong Lee Yang-Kyu Choi |
| author_sort | Na-Won Kim |
| collection | DOAJ |
| description | Carcinogenicity tests predict the tumorigenic potential of various substances in the human body by studying tumor induction in experimental animals. There is a need for studies that explore the use of FVB/N-Trp53em2Hwl/Korl (FVB-Trp53+/-) mice, created by TALEN-mediated gene targeting in Korea, in carcinogenicity tests. This study was performed to determine whether FVB-Trp53+/- mice are a suitable model for short-term carcinogenicity studies. To compare the carcinogenicity at different concentrations, 25, 50, and 75 mg/kg of N-methyl-N-nitrosourea (MNU), a known carcinogen, were administered intraperitoneally to FVB-Trp53+/- and wild-type male mice. After 26 weeks, the survival rate was significantly reduced in FVB-Trp53+/- mice compared to the wild-type mice in the 50 and 75 mg/kg groups. The incidence of thymic malignant lymphoma (TML) in the 50 and 75 mg/kg groups was 54.2 and 59.1% in FVB-Trp53+/- male mice, respectively. TML metastasized to the lungs, spleen, lymph nodes, liver, kidney, and heart in FVB-Trp53+/- male mice. Furthermore, the incidence of primary lung tumors, such as adenomas and adenocarcinomas, was 65.4, 62.5, and 45.4% in the FVB-Trp53+/- mice of the 25, 50, and 75 mg/kg groups, respectively. The main tumor types in FVB-Trp53+/- mice were TML and primary lung tumors, regardless of the dose of MNU administered. These results suggest that systemic tumors may result from malfunctions in the p53 gene and pathway, which is an important factor in the pathogenesis of human cancers. Therefore, FVB-Trp53 heterozygous mice are suitable for short-term carcinogenicity tests using positive carcinogens, and that the best result using MNU, a positive carcinogen, might have a single dose of 50 mg/kg. |
| first_indexed | 2024-04-09T23:17:59Z |
| format | Article |
| id | doaj.art-e0fb2513e72544bcb573a8e985e49102 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-09T23:17:59Z |
| publishDate | 2023-01-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS ONE |
| spelling | doaj.art-e0fb2513e72544bcb573a8e985e491022023-03-22T05:31:21ZengPublic Library of Science (PLoS)PLoS ONE1932-62032023-01-01181e028021410.1371/journal.pone.0280214Short-term carcinogenicity study of N-methyl-N-nitrosourea in FVB-Trp53 heterozygous mice.Na-Won KimSun-Min SeoEun-Seon YooAh-Reum KangJi-Hun LeeJae-Hoon LeeByeong-Cheol KangHan-Woong LeeYang-Kyu ChoiCarcinogenicity tests predict the tumorigenic potential of various substances in the human body by studying tumor induction in experimental animals. There is a need for studies that explore the use of FVB/N-Trp53em2Hwl/Korl (FVB-Trp53+/-) mice, created by TALEN-mediated gene targeting in Korea, in carcinogenicity tests. This study was performed to determine whether FVB-Trp53+/- mice are a suitable model for short-term carcinogenicity studies. To compare the carcinogenicity at different concentrations, 25, 50, and 75 mg/kg of N-methyl-N-nitrosourea (MNU), a known carcinogen, were administered intraperitoneally to FVB-Trp53+/- and wild-type male mice. After 26 weeks, the survival rate was significantly reduced in FVB-Trp53+/- mice compared to the wild-type mice in the 50 and 75 mg/kg groups. The incidence of thymic malignant lymphoma (TML) in the 50 and 75 mg/kg groups was 54.2 and 59.1% in FVB-Trp53+/- male mice, respectively. TML metastasized to the lungs, spleen, lymph nodes, liver, kidney, and heart in FVB-Trp53+/- male mice. Furthermore, the incidence of primary lung tumors, such as adenomas and adenocarcinomas, was 65.4, 62.5, and 45.4% in the FVB-Trp53+/- mice of the 25, 50, and 75 mg/kg groups, respectively. The main tumor types in FVB-Trp53+/- mice were TML and primary lung tumors, regardless of the dose of MNU administered. These results suggest that systemic tumors may result from malfunctions in the p53 gene and pathway, which is an important factor in the pathogenesis of human cancers. Therefore, FVB-Trp53 heterozygous mice are suitable for short-term carcinogenicity tests using positive carcinogens, and that the best result using MNU, a positive carcinogen, might have a single dose of 50 mg/kg.https://doi.org/10.1371/journal.pone.0280214 |
| spellingShingle | Na-Won Kim Sun-Min Seo Eun-Seon Yoo Ah-Reum Kang Ji-Hun Lee Jae-Hoon Lee Byeong-Cheol Kang Han-Woong Lee Yang-Kyu Choi Short-term carcinogenicity study of N-methyl-N-nitrosourea in FVB-Trp53 heterozygous mice. PLoS ONE |
| title | Short-term carcinogenicity study of N-methyl-N-nitrosourea in FVB-Trp53 heterozygous mice. |
| title_full | Short-term carcinogenicity study of N-methyl-N-nitrosourea in FVB-Trp53 heterozygous mice. |
| title_fullStr | Short-term carcinogenicity study of N-methyl-N-nitrosourea in FVB-Trp53 heterozygous mice. |
| title_full_unstemmed | Short-term carcinogenicity study of N-methyl-N-nitrosourea in FVB-Trp53 heterozygous mice. |
| title_short | Short-term carcinogenicity study of N-methyl-N-nitrosourea in FVB-Trp53 heterozygous mice. |
| title_sort | short term carcinogenicity study of n methyl n nitrosourea in fvb trp53 heterozygous mice |
| url | https://doi.org/10.1371/journal.pone.0280214 |
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