Transcriptomics does not show adverse effects of beta-carotene in A/J mice exposed to smoke for 2 weeks.
Beta-carotene (betaC) supplementation in smokers was unexpectedly associated with increased incidence of lung cancer versus smoking alone. We performed a study in A/J mice to explore possible betaC/cigarette smoke (CS) interactions potentially influencing lung cancer risk in smokers. A/J mice received a diet containing 120 or 600 ppm betaC for six weeks, and exposed to mainstream CS (140 mg total suspended particulates/m(3)) during the last two weeks. Lung transcriptomics analysis revealed that CS induced drug metabolism, oxidative stress, extracellular matrix (ECM) degradation, inflammation markers, and apoptosis. betaC reduced CS-induced inflammation markers and ECM degradation. betaC modulated the CS effect on apoptosis without a clear pro- or anti-apoptotic trend. betaC alone induced only minor changes of gene expression. In conclusion, betaC/CS interactions caused gene regulations in lungs. CS was the main effector. The gene regulations overall did not indicate that betaC exacerbated CS effects. Dose-dependency of betaC effects was minor and not detectable by genome-wide data mining.
Kuntz
Emmanuelle
E
DSM Nutritional Products, Human Nutrition and Health, PO Box 3255, Building 241/421, CH-4002 Basel, Switzerland.
Borlak
Jürgen
J
Riss
Georges
G
Aebischer
Claude-Pierre
CP
Bachmann
Heinrich
H
Seifert
Nicole
N
Hunziker
Petra Buchwald
PB
Sölle
Dörte
D
Hunziker
Willi
W
Goralczyk
Regina
R
Wertz
Karin
K
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004781:Environmental Exposure; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D020543:Proteome / Q000378:metabolism*; D013638:Tars / Q000494:pharmacology*; D014028:Tobacco Smoke Pollution; D014157:Transcription Factors / Q000378:metabolism*; D019207:beta Carotene / Q000008:administration & dosage*
D020543:Proteome; D013638:Tars; D014028:Tobacco Smoke Pollution; D014157:Transcription Factors; C024746:tobacco tar; D019207:beta Carotene