Quantitative analysis of constitutive and 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced cytochrome P450 1B1 expression in human lymphocytes

Citation
Dl. Spencer et al., Quantitative analysis of constitutive and 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced cytochrome P450 1B1 expression in human lymphocytes, CANC EPID B, 8(2), 1999, pp. 139-146
Citations number
35
Categorie Soggetti
Oncology,"Onconogenesis & Cancer Research
Journal title
CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
ISSN journal
10559965 → ACNP
Volume
8
Issue
2
Year of publication
1999
Pages
139 - 146
Database
ISI
SICI code
1055-9965(199902)8:2<139:QAOCA2>2.0.ZU;2-Z
Abstract
Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD or dioxin) results in a broad spectrum of biological responses, including altered metabolism, di sruption of normal hormone signaling pathways, reproductive and development al effects, and cancer. Cytochrome P450 1B1 (CYP1B1) is a dioxin-inducible gene that is active in the formation of 4-hydroxyestradiol, a potentially g enotoxic catechol estrogen, Therefore, the analysis of CYP1B1 in humans may be useful in establishing relationships between dioxin exposure and advers e health effects. In this study, we examined the expression of CYP1B1 in hu man peripheral blood lymphocytes of unexposed individuals using a quantitat ive reverse transcription-PCR method. Absolute CYP1B1 RNA levels varied mor e than 30-fold in uncultured mononuclear cells obtained from 10 individuals . In vitro treatment of mitogen-stimulated lymphocytes with TCDD for 1-5 da ys of culture resulted in a peak induction of CYP1B1 after 3 days. The indu ction of CYP1B1 RNA levels after 3 days of culture was dose-dependent, exhi bited a maximum response above 10 nM TCDD, and varied greatly among differe nt individuals. However, the half maximal dose required for this induction was similar between individuals and comparable to that observed in the MCF- 7 and HepG2 human cell lines, These observations indicate that CYP1B1 exhib its variable constitutive expression and is inducible in vitro by TCDD in h uman lymphocytes and that the magnitude of induction varies within the popu lation. These data define the suitability of CYP1B1 for use as a mechanisti cally based biomarker in ongoing molecular epidemiological studies of human populations exposed to dioxins and related chemicals that bind the aromati c hydrocarbon receptor.