Rw. West et Kl. Rowland, IN-VITRO TRANSFORMATION POTENTIAL OF N-POLYCYCLIC AROMATIC-HYDROCARBONS IN RAT TRACHEAL EPITHELIAL-CELLS, Toxicology in vitro, 8(2), 1994, pp. 301-307
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.