Occupational exposure to polycyclic aromatic hydrocarbons suppresses constitutive expression of CYP1B1 on the transcript level in human leukocytes.
Expression patterns of the cytochromes P450 CYP1A1 and CYP1B1 have been analyzed on the transcript level in leukocytes of persons (n = 30) occupationally exposed to polycyclic aromatic hydrocarbons (PAH). To assess effects on expression levels results were compared with data obtained from a non-exposed control group (n = 68). CYP1B1 transcripts can be detected in all subjects of the control group but vary largely in their levels (factor 35). Statistical analysis shows that this variability is neither due to the age of the persons nor due to cigarette smoking. Furthermore, there is no difference in expression levels between genders. In contrast to CYP1B1, CYP1A1 is detectable in only 14% of the subjects. People involved in graphite electrode production and exposed to PAH show largely decreased CYP1B1 transcript levels. In 67% of the subjects, CYP1B1 is no more detectable at all. Vice versa, expression of CYP1A1 is increased in exposed persons so that 80% become positive for CYP1A1 vs. 14% of the control group. The results show that occupational exposure to PAH apparently leads to effect-relevant internal doses. Both, suppression of CYP1B1 and induction of CYP1A1 in leukocytes can be used as exposure parameters proving both enzymes to be suitable biomarkers of exposure. The suppression of CYP1B1 is an unexpected effect which needs further investigation. It is discussed that CYP1B1 and CYP1A1 indeed share a common Ah receptor mediated transcriptional regulation but that differences in promoter structure of the two genes and tissue-specific expression profiles of transcription factors may cause a differential expression behaviour.
Abteilung für Hygiene, Sozial- und Umweltmedizin, Ruhr-Universität Bochum, Bochum, Germany.
Friederike
F
Lemm
Michael
M
Wilhelm
Peter H
PH
Roos
D000328:Adult; D000368:Aged; D001189:Aryl Hydrocarbon Hydroxylases; D015415:Biomarkers; D016022:Case-Control Studies; D019363:Cytochrome P-450 CYP1A1 / Q000097:blood; D065633:Cytochrome P-450 CYP1B1; D003577:Cytochrome P-450 Enzyme System / Q000097:blood*; D015536:Down-Regulation; D005260:Female; D005858:Germany; D006801:Humans; D007962:Leukocytes / Q000378:metabolism*; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D016273:Occupational Exposure / Q000009:adverse effects / Q000032:analysis*; D011084:Polycyclic Aromatic Hydrocarbons / Q000009:adverse effects / Q000032:analysis*; D018709:Statistics, Nonparametric; D014158:Transcription, Genetic
D015415:Biomarkers; D011084:Polycyclic Aromatic Hydrocarbons; D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D019363:Cytochrome P-450 CYP1A1; D065633:Cytochrome P-450 CYP1B1