In vivo mutagenesis in the lungs of gpt-delta transgenic mice treated intratracheally with 1,6-dinitropyrene.
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)x10(-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.
Research Center for Environmental Risk, National Institute for Environmental Studies, Ibaraki, Japan.
Akiko H
AH
Hashimoto
Kimiko
K
Amanuma
Kyoko
K
Hiyoshi
Hirohisa
H
Takano
Ken-ichi
K
Masumura
Takehiko
T
Nohmi
Yasunobu
Y
Aoki
D000393:Air Pollutants / Q000633:toxicity; D000818:Animals; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics*; D008168:Lung / Q000187:drug effects*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D016296:Mutagenesis; D009153:Mutagens / Q000633:toxicity*; D009154:Mutation; D011721:Pyrenes / Q000633:toxicity*; D017422:Sequence Analysis, DNA
D000393:Air Pollutants; D009153:Mutagens; D011721:Pyrenes; C033309:1,6-dinitropyrene; D007041:Hypoxanthine Phosphoribosyltransferase