Induction of ornithine decarboxylase in hamster tracheal epithelial cells exposed to asbestos and 12-O-tetradecanoylphorbol-13-acetate.

Crocidolite and chrysotile asbestos and the tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA), induce ornithine decarboxylase (ODC) in hamster trachéalepithelial cells (HTEB). When added at the time cells were plated, non-growthinhibitory amounts of crocidolite (0.64 to 1.28 ,ug/sq cm) and chrysotile (0.064 to 0.13 fig/sq cm) asbestos increased ODC activity 2to 3-fold after 24 to 30 hr. The effect was dose dependent. The nonfibrous mineral hematite (0.64 to 1.28 ¿ig/ sq cm) had no effect. Asbestos-stimulated induction did not occur in confluent monolayers unless fresh medium was added simultaneously. Under these conditions, both crocidolite (3-fold increase) and chrysotile (4-fold increase) induced ODC. TPA (0.1 jug/ml medium) produced a rapid, transient in crease in ODC activity in both logarithmically growing (6-fold increase) and confluent (30-fold increase) HTE-B. When TPA and fresh medium were combined, a synergistic effect was noted both in 24-hr cultures (22-fold increase) and at confluency (72to 92-hr cultures; 170-fold increase). The addition of asbestos and TPA alone had no effect on [3H]thymidine incorporation in confluent monolayers; however, a significant mitogenic response was observed when they were added with fresh medium. Under these circumstances, the cells appeared morphologically transformed. The ability of asbestos to induce ODC and influence prolif eration of HTE-B is consistent with the results of previous observations in our laboratory. These studies indicate that asbestos is producing a constellation of changes warranting its classification as a tumor promoter in the respiratory tract.