Mutagenicity testing of organic extracts of diesel exhaust particles after fractionation and recombination

Østby, Lene; Engen, Solveig; Melbye, Alf; Eide, Ingvar

doi:10.1007/s002040050392

Cited by 24 publications

(11 citation statements)

References 24 publications

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“…The mutagenicity of DEP extracts has been evaluated in vitro using Salmonella typhimurium TA98 assay without an exogenous metabolic activation system (S9 mixture), in which frameshift mutations were found to predominate [Salmeen et al, 1984;Østby et al, 1997;Rivedal et al, 2003]. Although we demonstrated the mutagenicity of DE in vivo using Big Blue 1 rats [Sato et al, 2000], further studies on its pulmonary effects are required for an assessment of the health risks of air pollution.…”

Section: Introductionmentioning

confidence: 90%

Mutations in the lungs of gpt delta transgenic mice following inhalation of diesel exhaust

Hashimoto

Amanuma

Hiyoshi

et al. 2007

Environ and Mol Mutagen

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Diesel exhaust (DE) is a major airborne pollutant of urban areas. It contains various polycyclic aromatic hydrocarbons (PAH) and nitrated PAHs. In this study, gpt delta mice were treated with inhalation of 1 or 3 mg m(-3) DE, or a single intratracheal instillation of diesel exhaust particles (DEP) or DEP extract. In the lungs of mice treated with inhalation of 3 mg m(-3) DE for 12 weeks, the mutant frequency (MF) was 3.2-fold higher than that of the control group (1.90 x 10(-5) and 0.59 x 10(-5), respectively). An instillation of DEP and DEP extract resulted in a significant dose-dependent linear increase in MF. In mice treated with 0.5 mg DEP and 0.2 mg DEP extract, the MFs were 3.0- and 2.7-fold higher than that of the control group, respectively. The mutagenic potency (MF mg(-1)) of DEP extract (5.6 x 10(-5)) was double that of DEP (2.7 x 10(-5)), suggesting that the mutagenicity of the latter is derived primarily from compounds in the extract, which itself is responsible for ca. 50% of the weight of DEP. G:C-->A:T transitions were the predominant gpt mutation induced by all three treatments and G:C-->T:A transversions were induced by DEP and DEP extract. Guanine bases centered in nucleotide sequences such as GGA, TGA, CGG, and CGT were the major mutation targets of all three treatments. Thus, our results suggest that the mutagens contained in DEP such as PAH and nitrated PAHs induce mutations and may be responsible for carcinogenesis caused by inhalation of DE.

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Section: Introductionmentioning

confidence: 90%

Mutations in the lungs of gpt delta transgenic mice following inhalation of diesel exhaust

Hashimoto

Amanuma

Hiyoshi

et al. 2007

Environ and Mol Mutagen

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“…The traditional way to handle non-linear problems in chemometrics has been to extend the X matrix explicitly by some function φ(X), for instance to incorporate quadratic terms [8,9] or lower-order polynomial terms. If more complex transformations are required, however, the dimensionality of φ(X) may be a limiting factor.…”

Section: Discussionmentioning

confidence: 99%

“…A common strategy has been to explicitly extend X according to a lower-order polynomial function, incorporating e.g. quadratic terms [8,9]. In general terms, the original data is transformed from the input space X ∈ R K into a higher-dimensional feature space F ⊆ R K * by a mapping function φ(·), defined as x i ∈ R K → φ(x i ) ∈ F ⊆ R K * ∀i = 1 .…”

Section: Introductionmentioning

confidence: 99%

Kernel‐based orthogonal projections to latent structures (K‐OPLS)

Rantalainen

Bylesjö

Cloarec

et al. 2007

Journal of Chemometrics

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The orthogonal projections to latent structures (OPLS) method has been successfully applied in various chemical and biological systems for modeling and interpretation of linear relationships between a descriptor matrix and response matrix. A kernel-based reformulation of the original OPLS algorithm is presented where the kernel Gram matrix is utilized as a replacement for the descriptor matrix. This enables usage of the 'kernel trick' to efficiently transform the data into a higherdimensional feature space where predictive and response-orthogonal components are calculated. This strategy has the capacity to improve predictive performance considerably in situations where strong non-linear relationships exist between descriptor and response variables while retaining the OPLS model framework. We put particular focus on describing properties of the rearranged algorithm in relation to the original OPLS algorithm. Four separate problems, two simulated and two real spectroscopic data sets, are employed to illustrate how the algorithm enables separate modeling of predictive and response-orthogonal variation in the feature space. This separation can be highly beneficial for model interpretation purposes while providing a flexible framework for supervised regression.

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“…Recently, a new strategy for the evaluation of complex mixtures was presented (45,74). The new approach is based on fractionation and recombination of the mixture in combination with the use of a mixture design.…”

Section: Fraciionation and Recombination Of Mixtures Plus Mixture Designmentioning

confidence: 99%

Toxicology of chemical mixtures: international perspective.

Feron

Cassee

Groten

1998

Environ Health Perspect

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In the United States, research programs on the toxicology of chemical mixtures have existed for several decades. These programs vary from real-life case studies (e.g., on contaminated soil or lakes, recycled drinking water, dioxins, diesel exhaust, coal tars, and chemicals released from hazardous waste sites) to the development of methods for the safety evaluation and risk assessment of both simple and complex mixtures such as new approaches for identification of genotoxic components in complex mixtures and the weight-of-evidence (WOE) approach, using interaction data in component-based risk assessment of mixtures (1-5). Moreover, in the United States, programs on more basic issues in mixture toxicology include physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) modeling of mixtures (6-8), the use of physicochemical concepts to mechanistic elucidation of toxicologic interactions (9), the development of statistical designs for experimental studies of mixtures (10-13),

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Mutagenicity testing of organic extracts of diesel exhaust particles after fractionation and recombination

Cited by 24 publications

References 24 publications

Mutations in the lungs of gpt delta transgenic mice following inhalation of diesel exhaust

Mutations in the lungs of gpt delta transgenic mice following inhalation of diesel exhaust

Kernel‐based orthogonal projections to latent structures (K‐OPLS)

Toxicology of chemical mixtures: international perspective.

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