Molecular analysis of hypoxanthine phosphoribosyl transferase mutants induced by glycidyl 1-naphthyl ether in mouse spleen cells in vivo
Autor: | R. S. Tan, Joseph E. Sinsheimer, E. H. Y. Chu |
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Rok vydání: | 1993 |
Předmět: |
Male
Hypoxanthine Phosphoribosyltransferase Epidemiology Base pair Health Toxicology and Mutagenesis Molecular Sequence Data Mutant Naphthols Biology Polymerase Chain Reaction Frameshift mutation Mice Exon chemistry.chemical_compound Complementary DNA Animals Point Mutation Amino Acid Sequence Lymphocytes Codon Thioguanine Gene Cells Cultured Genetics (clinical) Hypoxanthine Base Sequence DNA Molecular biology Mice Inbred C57BL Oligodeoxyribonucleotides chemistry Biochemistry Hypoxanthine-guanine phosphoribosyltransferase Epoxy Compounds Spleen Mutagens |
Zdroj: | Environmental and Molecular Mutagenesis. 22:71-77 |
ISSN: | 1098-2280 0893-6692 |
Popis: | Treatment of C57BL/6J mice with an epoxide, glycidyl 1-naphthyl ether (GNE), resulted in an average of a 3.4-fold increase in frequency of 6-thioguanine-resistant mutants of mouse spleen T-lymphocytes. In similar experiments with the epoxide trichloropropylene oxide, no increase in mutant frequency was found. To determine the kind and location of mutations in the coding region of the hypoxanthine phosphoribosyl transferase (HPRT) gene, 26 GNE-induced mutants and 17 spontaneous mutants were analyzed by direct sequencing of polymerase chain reaction amplified cDNA. Among the GNE-induced mutants, HPRT cDNA was present in 22, while that from 4 could not be detected. Among the spontaneous mutants, HPRT cDNA was present in 15 and absent in 2. Among GNE-induced mutants, base substitution in HPRT occurred in 15 of 22 mutants analyzed. Nine of 15 base substitutions involved TA base pairs, primarily TACG transitions. Base substitutions were found throughout exons 3–7 but 46% of substitutions were located in exon 3 and one frameshift mutation involving a GC base pair in exon 3 was also observed. Among the spontaneous mutants, base substitutions of HPRT occurred in 7 of 15 mutants analyzed with 6 of 7 base substitutions involving a TA base pair and another 2 of the 15 mutants showed a 4 base pair deletion. The base substitution spectrum in GNE-induced mutants was different from that of the spontaneous mutants. © 1993 Wiley-Liss, Inc. |
Databáze: | OpenAIRE |
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