Multi-laboratory evaluation of 1,3-propane sultone, N-propyl-N-nitrosourea, and mitomycin C in the Pig-a mutation assay in vivo

Publication date: July 2018Source: Mutation Research/Genetic Toxicology and Environmental Mutagenesis, Volume 831Author(s): Young-Shin Chung, Bumsoo Pak, Sehee Han, Jiyeon Lee, Jiyoung Kim, Seng-Min Back, Cho-Rong Park, Su-Hwan Kim, Jong-Kwon LeeAbstractThe mutagenic potencies of 1,3-propane sultone (PS), N-propyl-N-nitrosourea (PNU), and mitomycin C (MMC) were investigated in three independent laboratories in Korea using the Pig-a assay in vivo. Sprague-Dawley rats were treated with vehicle or test substance on three consecutive days. Blood samples were collected for measuring Pig-a mutant phenotypes (CD59-deficient erythrocytes, RBCCD59−; CD59-deficient reticulocytes, RETCD59−) on days −1, 15, and 29 after the first treatment. In some studies, blood was collected for determining DNA damage (comet assay) on day 3 and measuring micronucleated reticulocytes (MN-RET) on day 4. Treatment with the alkylating agents PS and PNU induced dose-dependent increases in the frequency of RBCCD59− on days 15 and 29, and caused maximum elevations in the frequency of RETCD59− on day 15. Inter-laboratory comparison of the day 29 Pig-a assay data confirmed the mutagenic potencies of PS and PNU, and showed good agreement among the test sites. Treatment with the DNA cross-linker MMC induced increases in the frequencies of RBCCD59− and RETCD59− on days 15 and 29 (all three laboratories). MN-RETs increased significantly in animals treated with PS, PNU, or MMC, but biologically signifi...
Source: Mutation Research Genetic Toxicology and Environmental Mutagenesis - Category: Genetics & Stem Cells Source Type: research