IN-VITRO TRANSFORMATION POTENTIAL OF N-POLYCYCLIC AROMATIC-HYDROCARBONS IN RAT TRACHEAL EPITHELIAL-CELLS

Nitro-polycyclic aromatic hydrocarbons (nitro-PAHs) are environmental contaminants and potential human airway carcinogens. Agents of this cl ass show a wide range of potencies for toxicity, mutagenicity and carc inogenicity that are associated with the structure of the PAH and the position of the nitro group. In order to evaluate the effect of nitro substitution on in vitro biological activity, the cytotoxicity and tra nsformation potential of two parent PAHs, pyrene and chrysene, and a s eries of nitro derivatives were examined in the rat tracheal epithelia l (RTE) cell system. The nitro derivatives, but not pyrene or chrysene , produced dose-dependent decreases in the colony forming efficiency o f the RTE cells. The most cytotoxic agents were 1,6-dinitropyrene and 6-nitrochrysene with ED(50)s of 1.6 mu M and 5.9 mu M, respectively, f ollowed by 4-nitropyrene and 1-nitropyrene with ED(50)s of 26.3 mu M a nd 44.5 mu M, respectively. These compounds were evaluated for transfo rmation potential at three treatment levels that spanned the cytotoxic range, and the assays were scored for morphologically transformed pre neoplastic colonies. The control or spontaneous transformation frequen cy in this series of experiments was 1.79 +/- 0.47 (x 10(-4)). 6-Nitro chrysene and 1,6-dinitropyrene were the only compounds that produced t ransformation frequencies (12.17 x 10(-4) and 9.68 x 10(-4), respectiv ely) that were statistically different from control. The maximum trans formation frequencies of the compounds were compared with published da ta for liver tumorigenicity in the newborn mouse assay. The orders for tumorigenicity and transformation were the same (1,6-dinitropyrene > 4-nitropyrene > 1-nitropyrene U pyrene and 6-nitrochrysene > chrysene) , and the relative potencies of the compounds were similar in the two assays. These results suggest that RTE cells are capable of metabolizi ng nitro-PAHs to reactive products, and that, within this limited clas s of compounds, in vitro transformation data in the RTE cell system ma y be correlated with tumorigenicity in animal studies.