Constitutive CYP1B1 mRNA expression in human blood mononuclear cells in relation to gender, genotype, and environmental factors.
Cytochromes P4501B1 (CYP1B1) and P4501A1 (CYP1A1) are involved in the metabolic activation of many polycyclic aromatic hydrocarbons (PAH). To investigate the variability of these enzymes in humans a long-term study of the constitutive mRNA expression in peripheral blood mononuclear cells (PBMC) was initiated. Blood samples were collected from 16 volunteers of both sexes every second month during a 20-month period in 1999 and 2000. mRNA expression was quantified using a competitive reverse transcription-PCR method. The monocyte content in PBMC was determined using a fluorescence-activated cell sorter. To study the effect of genotype, polymorphisms in CYP1B1, CYP1A1, and glutathione transferase M1 (GSTM1) were determined by PCR-based methods. Information about environmental PAH exposure and solar radiation was obtained through questionnaires and solar radiation records. Since the levels of CYP1A1 mRNA were found to be extremely low (at or below the detection level), only CYP1B1 mRNA levels were quantified. The maximum range of CYP1B1 mRNA expression across different blood collection time points and subjects was 30-fold (1670-49,900 CYP1B1 mRNA molecules/10(6) beta-actin mRNA molecules). The individual average levels of expression ranged from 8520 to 12,700 CYP1B1 mRNA molecules/10(6) beta-actin mRNA molecules (a 2.3-fold variation), with an average level of 12,700 CYP1B1 mRNA molecules/10(6) beta-actin mRNA molecules. A pronounced variation in CYP1B1 expression between the different time points of blood collection was observed. The intraindividual variation of CYP1B1 expression during the 20-month study period was from 3- to 21-fold (average 9-fold) and the average interindividual fold variation, at one time point, was 8 (range 3-16). An association between solar radiation records and CYP1B1 mRNA expression was suggested. This correlation was significant for the year 2000 (rs=0.30, P=0.012). No or weak effects of age, gender, monocyte content in total PBMC, recent PAH exposure, or genetic polymorphisms in CYP1B1, CYP1A1, or GSTM1 were observed.
Tuominen
Rainer
R
Unit of Work Environment Toxicology, Institute of Environmental Health, Karolinska Institutet, Box 210, SE-171 77 Stockholm, Sweden.
Warholm
Margareta
M
Möller
Lennart
L
Rannug
Agneta
A
D000328:Adult; D001189:Aryl Hydrocarbon Hydroxylases / Q000096:biosynthesis* / Q000235:genetics; D065633:Cytochrome P-450 CYP1B1; D004777:Environment; D005260:Female; D005838:Genotype; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000201:enzymology*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000096:biosynthesis; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012737:Sex Factors
D012333:RNA, Messenger; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D065633:Cytochrome P-450 CYP1B1