PARENT SESSION

2C - Biomarkers
Poster Hall
8:30 AM - Tuesday, 29 April 2003
Chair: Hansen, P.D.¹, ¹
Co-chair: Vindimian, E.², ²

(TUP/109) In vitro inhibition of GJIC in WB-F344 cells by polar derivatives of PAHs.

Blaha, Ludek^{1, 2}, Kapplova, Petra², Machala, Miroslav², ¹ RECETOX, Masaryk University, Brno, Czech Republic, CZ² Veterinary Research Institute, Brno, Czech Republic, CZ

ABSTRACT- Gap-junctional intercellular communication (GJIC) is considered to be crucial mechanism involved in several physiological and pathological events including cellular differentiation, apoptosis or tumorigenesis. Detection of GJIC inhibition in vitro was shown to be an important biomarker of tumor promoting potencies of several xenobiotics including environmental pollutants, such as PCBs, PAHs or pesticides. We have studied acute inhibitory effects on GJIC (30 min) by polar organic compounds which are found in high concentration in air as well as other environmental matrices. The potencies to inhibit GJIC in normal rat liver epithelial cells WB-F344 were measured by scrape-loading/dye transfer technique and epifluorescence microscopy. Twenty nitro-, oxo- and aza-derivatives of polycyclic aromatic hydrocarbons (PAHs) and respective unsubstituted compounds were assessed. Potency to inhibit GJIC was determined by several structural and physicochemical characteristics: 1) low molecular weight (MW) PAHs (indene and naphthalene) and corresponding polar derivatives did not inhibited GJIC up to 100 micromolar concentrations (muM); 2) although the bay or bay-like region formed by methyl- or chlorine- substituents was previously shown to be important determinant of GJIC inhibiting PAHs, corresponding polar nitro- or oxo- derivatives had nonsignificant effects; 3) the only significantly inhibiting polar derivatives of PAHs were 3- and 9-monohydroxyderivatives of benzo[a]pyrene (BaP) which inhibited GJIC more than did the BaP. The inhibitory effect of all active compounds was observed within the same concentration range (IC50=28-48 muM), suggesting similar mechanism of action. In comparison with parent unsubstituted PAHs (Blaha et al., Toxicol Sci 65(1): 43-51) environmentaly occuring polar derivatives seem to elicit weak tumor promoting potencies in the in vitro assay for inhibition of GJIC. Acknowledgements: The work was supported by GACR 525/00/D101 grant.

Key words: oxo-PAHs, GJIC, nitro-PAHs, aza-PAHs