In vivo mutagenesis in the lungs of gpf-delta transgenic mice treated intratracheally with 1,6-dinitropyrene

• Published in: Environmental and molecular mutagenesis Vol. 47; no. 4; pp. 277 - 283
• Main Authors: Hashimoto, AH, Amanuma, K, Hiyoshi, K, Takano, H, Masumura, K-I, Nohmi, T, Aoki, Y
• Format: Journal Article
• Language: English
• Published: 01.05.2006
• ISSN: 0893-6692
• DOI: 10.1002/em.20204

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 gpf-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 plus or minus 0.16) x 10 super(-) super(5)). The major mutations induced by 1,6-DNP included G:C arrow right A:T transitions, G:C arrow right T:A transversions, and 1-base deletions. Among the G:C arrow right 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.