Differential induction of CYP1A1 in duodenum, liver and kidney of rats after oral intake of soil containing polycyclic aromatic hydrocarbons.

作者: Peter Roos

DOI: 10.1007/S00204-001-0317-3

关键词:

摘要: We have analyzed the induction of cytochrome P450 enzyme CYP1A1 as a biomarker effect in duodenum, liver and kidney rats after oral intake contaminated soil particles. The samples originated from industrial sites were with polycyclic aromatic hydrocarbons (PAH) to variable extents, ranging 60 4700 mg PAH/kg soil. Soil administered for one week mixture commercial rodent diets. After exposure, microsomes several organs prepared CYP1A1, enzymatically by Western blots. All soils led duodenal mucosa cells, regardless their extent contamination, showing that relevant doses mobilized gastrointestinal tract adsorbed. Subsequent distribution non-metabolized compounds is indicated liver. However, some did not lead response liver, due quantitative qualitative contaminant composition. In accordance previous results, there sigmoidal dose-response relationship between hepatic levels contamination higher condensates PAH. contrast, duodenum appeared be hyperbolic correlated well amounts total Highly soil, being nearly devoid PAH, pronounced but failed induce Successful passage contaminants through intestinal barrier compartment shown increased expression kidney. Compared induced those are much lower amount only about 1/20 values high potential. Hence, PAH leads differential patterns rats. observations raise questions concerning role primary metabolism preventing contaminant-dependent hazardous effects, significance expressions carcinogenic processes tissues.

参考文章(43)
Carrie L. Hayes, Shantu Amin, Tsutomu Shimada, Hiroshi Yamazaki, Thomas R. Sutter, Thomas R. Sutter, F. Peter Guengerich, F. Peter Guengerich, Stephen S. Hecht, Activation of chemically diverse procarcinogens by human cytochrome P-450 1B1 Cancer Research. ,vol. 56, pp. 2979- 2984 ,(1996)
A. Lewis Farr, Oliver H. Lowry, Rose J. Randall, Nira J. Rosebrough, Protein Measurement with the Folin Phenol Reagent Journal of Biological Chemistry. ,vol. 193, pp. 265- 275 ,(1951)
Alycia K. Halladay, Michael M. Iba, Anna Sekowski, George C. Wagner, Hans Fisher, Paul E. Thomas, Jacqueline Fung, Yang Won Pak, Dose-dependent up-regulation of rat pulmonary, renal, and hepatic cytochrome P-450 (CYP) 1A expression by nicotine feeding. Drug Metabolism and Disposition. ,vol. 27, pp. 977- 982 ,(1999)
Tsuneo Omura, Ryo Sato, The Carbon Monoxide-binding Pigment of Liver Microsomes Journal of Biological Chemistry. ,vol. 239, pp. 2370- 2378 ,(1964) , 10.1016/S0021-9258(20)82244-3
Chandikumar S. Elangbam, Charles W. Quails, Robert L. Lochmiller, O-dealkylation of resorufin ethers as an indicator of hepatic cytochrome P-450 isoenzyme induction in the cotton rat (Sigmodon hispidus): A method for monitoring environmental contamination Bulletin of Environmental Contamination and Toxicology. ,vol. 47, pp. 23- 28 ,(1991) , 10.1007/BF01689448
M.T. Vincenzini, F. Favilli, M. Stio, T. Iantomasi, Intestinal glutathione transport system: a possible detoxication role. Biochimica et Biophysica Acta. ,vol. 1073, pp. 571- 579 ,(1991) , 10.1016/0304-4165(91)90232-6
J.C Kolars, P.B Watkins, R.M Merion, W.M Awni, First-pass metabolism of cyclosporin by the gut. The Lancet. ,vol. 338, pp. 1488- 1490 ,(1991) , 10.1016/0140-6736(91)92302-I
P. H. Roos, M. van Afferden, D. Strotkamp, D. Tappe, F. Pfeifer, W. G. Hanstein, Liver microsomal levels of cytochrome P450IA1 as biomarker for exposure and bioavailability of soil-bound polycyclic aromatic hydrocarbons Archives of Environmental Contamination and Toxicology. ,vol. 30, pp. 107- 113 ,(1996) , 10.1007/BF00211335