Tags

Type your tag names separated by a space and hit enter

Modulation of plasma lipid levels affects benzo[a]pyrene-induced DNA damage in tissues of two hyperlipidemic mouse models.
Environ Mol Mutagen. 2003; 42(4):243-9.EM

Abstract

The role of plasma lipids in the uptake, transportation, and distribution of lipophilic carcinogens like benzo[a]pyrene (B[a]P) remains unclear. Therefore, we studied the effects of dietary-modulated plasma lipids on B[a]P-induced DNA damage in several organs of two hyperlipidemic mouse models. Male apolipoprotein E (ApoE)*3-Leiden (n = 22) and ApoE knockout (ApoE-KO) mice (n = 20) were fed a high-fat cholesterol (HFC) diet or low-fat cholesterol (LFC; standard mouse chow) diet for 3 weeks, after which the animals were exposed to a single oral dose of 5 mg/kg bw B[a]P or vehicle and killed 4 days later. Plasma lipids were determined and DNA adducts were measured in aorta, heart, lung, liver, brain, and stomach. Total cholesterol and low-density lipoprotein (LDL) cholesterol were increased in all animals on a HFC diet, whereas a decrease of triglycerides was seen only in the ApoE-KO mice. In ApoE-KO mice on a normal diet, DNA-adduct levels were highest in aorta (10.8 +/- 1.4 adducts/10(8) nucleotides), followed by brain (7.8 +/- 1.3), lung (3.3 +/- 0.7), heart (3.1 +/- 0.6), liver (1.5 +/- 0.2) and stomach (1.2 +/- 0.2). In the ApoE*3-Leiden mice, adduct levels were equally high in aorta, heart, and lung (4.6 +/- 0.7, 5.0 +/- 0.5 and 4.6 +/- 0.4, respectively), followed by stomach (2.7 +/- 0.4), brain (2.3 +/- 0.2), and liver (1.7 +/- 0.2). In the ApoE-KO mice, the HFC diet intervention resulted in lower adduct levels in lung (2.1 +/- 0.2), heart (1.9 +/- 0.2), and brain (2.9 +/- 0.5), as compared with the LFC group. In contrast, a nonsignificant increase of adducts was found in aorta (13.1 +/- 1.5). A similar but nonsignificant trend was observed in the ApoE*3-Leiden mice. Multiple regression analysis showed that in aorta, DNA adducts were inversely related to plasma triglycerides (P = 0.004) and were also modulated by the ApoE genotype (P < 0.001). The results of the present study support further investigation into the role of dietary modulation of plasma lipids, ApoE, and polycyclic aromatic hydrocarbon exposure on the formation of DNA adducts in chronic degenerative diseases.

Authors+Show Affiliations

Department of Health Risk Analysis and Toxicology, University of Maastricht, Maastricht, The Netherlands.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

14673869

Citation

Curfs, Daniëlle M J., et al. "Modulation of Plasma Lipid Levels Affects Benzo[a]pyrene-induced DNA Damage in Tissues of Two Hyperlipidemic Mouse Models." Environmental and Molecular Mutagenesis, vol. 42, no. 4, 2003, pp. 243-9.
Curfs DM, Beckers L, Godschalk RW, et al. Modulation of plasma lipid levels affects benzo[a]pyrene-induced DNA damage in tissues of two hyperlipidemic mouse models. Environ Mol Mutagen. 2003;42(4):243-9.
Curfs, D. M., Beckers, L., Godschalk, R. W., Gijbels, M. J., & van Schooten, F. J. (2003). Modulation of plasma lipid levels affects benzo[a]pyrene-induced DNA damage in tissues of two hyperlipidemic mouse models. Environmental and Molecular Mutagenesis, 42(4), 243-9.
Curfs DM, et al. Modulation of Plasma Lipid Levels Affects Benzo[a]pyrene-induced DNA Damage in Tissues of Two Hyperlipidemic Mouse Models. Environ Mol Mutagen. 2003;42(4):243-9. PubMed PMID: 14673869.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Modulation of plasma lipid levels affects benzo[a]pyrene-induced DNA damage in tissues of two hyperlipidemic mouse models. AU - Curfs,Daniëlle M J, AU - Beckers,Linda, AU - Godschalk,Roger W L, AU - Gijbels,Marion J J, AU - van Schooten,Frederik J, PY - 2003/12/16/pubmed PY - 2004/2/13/medline PY - 2003/12/16/entrez SP - 243 EP - 9 JF - Environmental and molecular mutagenesis JO - Environ Mol Mutagen VL - 42 IS - 4 N2 - The role of plasma lipids in the uptake, transportation, and distribution of lipophilic carcinogens like benzo[a]pyrene (B[a]P) remains unclear. Therefore, we studied the effects of dietary-modulated plasma lipids on B[a]P-induced DNA damage in several organs of two hyperlipidemic mouse models. Male apolipoprotein E (ApoE)*3-Leiden (n = 22) and ApoE knockout (ApoE-KO) mice (n = 20) were fed a high-fat cholesterol (HFC) diet or low-fat cholesterol (LFC; standard mouse chow) diet for 3 weeks, after which the animals were exposed to a single oral dose of 5 mg/kg bw B[a]P or vehicle and killed 4 days later. Plasma lipids were determined and DNA adducts were measured in aorta, heart, lung, liver, brain, and stomach. Total cholesterol and low-density lipoprotein (LDL) cholesterol were increased in all animals on a HFC diet, whereas a decrease of triglycerides was seen only in the ApoE-KO mice. In ApoE-KO mice on a normal diet, DNA-adduct levels were highest in aorta (10.8 +/- 1.4 adducts/10(8) nucleotides), followed by brain (7.8 +/- 1.3), lung (3.3 +/- 0.7), heart (3.1 +/- 0.6), liver (1.5 +/- 0.2) and stomach (1.2 +/- 0.2). In the ApoE*3-Leiden mice, adduct levels were equally high in aorta, heart, and lung (4.6 +/- 0.7, 5.0 +/- 0.5 and 4.6 +/- 0.4, respectively), followed by stomach (2.7 +/- 0.4), brain (2.3 +/- 0.2), and liver (1.7 +/- 0.2). In the ApoE-KO mice, the HFC diet intervention resulted in lower adduct levels in lung (2.1 +/- 0.2), heart (1.9 +/- 0.2), and brain (2.9 +/- 0.5), as compared with the LFC group. In contrast, a nonsignificant increase of adducts was found in aorta (13.1 +/- 1.5). A similar but nonsignificant trend was observed in the ApoE*3-Leiden mice. Multiple regression analysis showed that in aorta, DNA adducts were inversely related to plasma triglycerides (P = 0.004) and were also modulated by the ApoE genotype (P < 0.001). The results of the present study support further investigation into the role of dietary modulation of plasma lipids, ApoE, and polycyclic aromatic hydrocarbon exposure on the formation of DNA adducts in chronic degenerative diseases. SN - 0893-6692 UR - https://www.unboundmedicine.com/medline/citation/14673869/Modulation_of_plasma_lipid_levels_affects_benzo[a]pyrene_induced_DNA_damage_in_tissues_of_two_hyperlipidemic_mouse_models_ L2 - https://doi.org/10.1002/em.10200 DB - PRIME DP - Unbound Medicine ER -