Differential induction of CYP1A1 in duodenum, liver and kidney of rats after oral intake of soil containing polycyclic aromatic hydrocarbons.
We have analyzed the induction of the cytochrome P450 enzyme CYP1A1 as a biomarker of effect in duodenum, liver and kidney of rats after oral intake of contaminated soil particles. The soil samples originated from industrial sites and were contaminated with polycyclic aromatic hydrocarbons (PAH) to variable extents, ranging from 60 to 4700 mg PAH/kg soil. Soil samples were administered for one week as a mixture with commercial rodent diets. After exposure, microsomes of several organs were prepared and analyzed for CYP1A1, enzymatically and by Western blots. All contaminated soils led to induction of CYP1A1 in duodenal mucosa cells, regardless of their extent of contamination, showing that relevant doses were mobilized in the gastrointestinal tract and adsorbed. Subsequent distribution of non-metabolized compounds is indicated by induction of CYP1A1 in the liver. However, some samples did not lead to a response in the liver, due to their quantitative and qualitative contaminant composition. In accordance with previous results, there is a sigmoidal dose-response relationship between induction of hepatic CYP1A1 levels and the soil contamination with higher condensates of PAH. In contrast, the response in the duodenum appeared to be hyperbolic and correlated well with the amounts of total PAH. Highly contaminated soil, being nearly devoid of higher condensates of PAH, led to pronounced induction in the duodenum but failed to induce CYP1A1 in the liver. Successful passage of contaminants through the intestinal barrier and the liver compartment is shown by increased CYP1A1 expression in the kidney. Compared with enzyme levels induced in the liver, those of the kidney are much lower and amount to only about 1/20 of the liver values for soils with high induction potential. Hence, oral PAH intake leads to differential induction patterns of CYP1A1 in duodenum, liver and kidney of rats. The observations raise questions concerning the role of the primary duodenal PAH metabolism in preventing contaminant-dependent hazardous effects, and of the significance of differential CYP1A1 expressions for carcinogenic processes in several tissues.
Roos
Peter H
PH
Medical Faculty, Arbeitskreis Biomarker und Fremdstoffwirkungen, Ruhr-University Bochum, Im Lottental 36, 4480-1 Bochum, Germany. peter.roos@ruhr-uni-bochum.de
D000818:Animals; D015415:Biomarkers / Q000032:analysis; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D004386:Duodenum / Q000187:drug effects / Q000201:enzymology*; D004790:Enzyme Induction; D007220:Industrial Waste / Q000009:adverse effects; D007668:Kidney / Q000187:drug effects / Q000201:enzymology*; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D011084:Polycyclic Aromatic Hydrocarbons / Q000032:analysis / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012987:Soil / Q000032:analysis; D012989:Soil Pollutants / Q000633:toxicity*
D015415:Biomarkers; D007220:Industrial Waste; D011084:Polycyclic Aromatic Hydrocarbons; D012987:Soil; D012989:Soil Pollutants; D019363:Cytochrome P-450 CYP1A1