Benzo[b]phenanthro[2,3-d]thiophene (BPT), an environmental carcinogen, is a more potent carcinogen than its carbon analog dibenz[a,h]anthracene. We have recently reported that BPT is metabolized by rodent liver microsomes to a number of metabolites including BPT sulfoxide and BPT 3,4-diol (a precursor of bay-region diol epoxide of BPT) ), and that BPT sulfoxide is 3 to 4-fold more mutagenic than BPT 3,4-diol in S. typhimurium strain TA100 (Chem. Res. Toxicol. 16, 2003, 1581; Mut. Res. 545, 2004, 11). Determining the capability of humans to metabolize BPT to its mutagenic/carcinogenic metabolites is important for assessing the human health risk associated with BPT. In the present study, we have investigated the metabolism of BPT by human lung epithelial BEAS-2B cells. These cells express PAH activating enzymes P450 1A1 and P450 1B1 and therefore represent a good human model for studying lung carcinogenesis because they are derived from lung epithelium which is a target organ for PAHs. The cells were cultured in LHC-9 medium in 150 mm2 petridishes to confluency (∼ 6 x 106 cells) and treated with BPT (2 μM) containing 2 μCi of [G-3H]-BPT for 24 and 48 h. Intracellular and extracellular BPT metabolites in the cells and medium were isolated by repeated ethyl acetate/acetone (2 : 1) extractions. BPT and its metabolites were analyzed by HPLC as described earlier (Chem. Res. Toxicol. 16, 2003, 1581). The data indicate that BEAS-2B cells were able to metabolize BPT. The extent to which BPT is metabolized to ethyl acetate extractable metabolites after 24 h and 48 h incubation was 5.17% and 11.49%, respectively. BPT phenols having retention times similar to that of 2-hydroxy- and 3-hydroxyBPT were the major metabolites (36-46%) at both 24 h and 48h. The percentage of BPT 3,4-diol, BPT 5,6-diol and BPT sulfoxide after 24 h (48 h) was 13.79 (15.00),16.45 (18.49), and 6.58 (9.46), respectively. BPT sulfoxide was not detected in quantifiable amounts in any of the samples. The data from these studies indicate that BEAS-2B cells are able to metabolize BPT to muagenic metabolites BPT sulfoxide and BPT 3,4-diol, and therefore human lung may be susceptible to BPT-induced carcinogenesis. Research supported in part by USEPA grant # R826192.

[Proc Amer Assoc Cancer Res, Volume 46, 2005]