MP20 'Omic' Technologies - Current and Future Applications to Environmental Toxicology
Monday, 14 November 2005: 8:00 AM - 6:30 PM in Exhibit Hall
(KAG-1116-228751) DNA microarray expression profiling of leukocyte-expressed genes in the mouse exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin.
Kagami, Y1, Mitsui, T2, Akane, H2, Maeda, S2, 1 Ecogenomics, Inc., Kurume, Fukuoka, Japan2 University of Yamanashi, Tamaho-cho, Yamanashi, Japan
ABSTRACT- Although exposure to dioxins and dioxin-like compounds causes variety of pathological adverse effects to human and wildlife, suitable molecular biomarkers for routine diagnostic analysis or risk assessment have not been discovered yet. As we developed a mouse cDNA microarray containing probes for 508 genes that were selected for their known or potential responsiveness to environmentally toxic compounds (e.g., estrogen-like and dioxin-like compounds), we carried out cDNA microarray gene expression profiling analysis of the C57BL/6 mouse leukocytes. In this analysis, the leukocyte mRNAs obtained from 8-week-old mice (five individuals from each sex), that were exposed to 5
g/kg-body weight of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), were compared with the leukocyte mRNAs from the unexposed 8-week-old mice (five individuals from each sex). Our approach was to discover acute transcriptional gene responses to TCDD in the leukocytes (single dose by gavage/day for three consecutive days, then blood sample was drawn at 72 hours after the last dose) rather than to find immunotoxicological responses from chronic low-dose exposure. In our short exposure-acute response study, we identified three TCDD-responsive genes in addition to cyp1A1 and cyp1B1, and those three genes were angiotensin II receptor type 2, matrix metalloproteinase 8, and prostaglandin-endoperoxide synthase 2 (cyclooxygenase-2). Interestingly, these genes did not only show TCDD-responsiveness but also showed sexually dimorphic responses. This result implied a potentially useful feature of the gender-specific biomarkers for the diagnostic measurement and/or risk assessment of the dioxin-like compounds.
Key words: dioxin, mouse, leukocyte, microarray