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In vivo mutagenesis in the lungs of gpt ‐delta transgenic mice treated intratracheally with 1,6‐dinitropyrene
Author(s) -
Hashimoto Akiko H.,
Amanuma Kimiko,
Hiyoshi Kyoko,
Takano Hirohisa,
Masumura Kenichi,
Nohmi Takehiko,
Aoki Yasunobu
Publication year - 2006
Publication title -
environmental and molecular mutagenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1
H-Index - 87
eISSN - 1098-2280
pISSN - 0893-6692
DOI - 10.1002/em.20204
Subject(s) - mutagen , mutagenesis , microbiology and biotechnology , mutant , mutation , frameshift mutation , in vivo , mutation frequency , chemistry , ratón , transgene , genetically modified mouse , biology , genetics , carcinogen , biochemistry , immunology , gene
1,6‐Dinitropyrene (1,6‐DNP) is a ubiquitous airborne pollutant found in diesel exhaust. In this study, mutagenesis was examined in the lungs of gpt ‐delta transgenic mice after intratracheal instillation of 0–0.1 mg 1,6‐DNP. In addition, the 1,6‐DNP‐induced gpt mutation spectrum was compared with that of control mice. A single intratracheal injection of 0–0.05 mg 1,6‐DNP resulted in significant dose‐dependent increases in mutant frequency; the induced mutant frequency declined at the 0.1 mg dose. The average lung mutant frequencies at doses of 0.025, 0.05, and 0.1 mg 1,6‐DNP were 2.9‐, 4.1‐, and 1.9‐times higher than for control mice ((0.50 ± 0.16) × 10 −5 ). The major mutations induced by 1,6‐DNP included G:C→A:T transitions, G:C→T:A transversions, and 1‐base deletions. Among the G:C→A:T transitions isolated from 1,6‐DNP‐treated mice, five (at nucleotide positions 64, 110, 115, 116, and 418) were observed in four or more animals. These positions therefore are potential hotspots for 1,6‐DNP mutation. The predominant frameshift mutations following 1,6‐DNP treatment included single base pair deletions at G:C (9/13 = 69%). The results of this study indicate that 1,6‐DNP is mutagenic for the lungs of mice. Environ. Mol. Mutagen., 2006. © 2006 Wiley‐Liss, Inc.