In vitro transformation and tumor promotion studies of styrene and styrene oxide.

The carcinogenic properties of styrene and styrene oxide were investigated using C3H/10T1/2C18 cells as a test system. In vitro transformation was not observed for either of the two chemicals; however, styrene oxide at three different concentrations enhanced the morphological transformation in the two-stage transformation assay. 0.1, 1 and 10 microM styrene oxide added twice weekly resulted in 32.4, 26.8 and 31.4 per cent of the dishes with one or more type III foci. Styrene and styrene oxide were only slightly toxic to the cells at the concentrations used. Styrene oxide did not affect the growth rate of the C3H/10T1/2 cells at 10 microM. However, 100 microM styrene oxide added to logarithmically growing cells caused a significant decrease in growth rate within 24 to 48 h. The tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate inhibited DNA synthesis approximately 60% 8 h after initiation of treatment. When styrene oxide at concentrations up to 100 microM was tested in a similar experiment, however, no significant effect was observed. Total RNA synthesis increased by 70% 1.5 h after initiation of treatment at 1 microM styrene oxide; this effect was not seen after 24 h. Styrene oxide at concentrations of 1 and 0.1 microM stimulated the incorporation of [3H]choline into cells by approximately 20% during a 2 h incubation, the major site of incorporation being the nuclear-associated endoplasmic reticulum.