Mechanisms of neoplastic transformation by quartz particles were studied, using the BALB/3T3/A31-1-1 mouse embryo cell line previously established as a quantitative model for cytotoxicity and transformation. The trans- forming activity of quartz particles was confirmed in several experiments, all showing a characteristic plateau in the dose-response curve at doses of 25 microg/cm square or higher, indicative of a rate- limiting factor. Inhibition of the transforming activity of quartz was demonstrated by concurrent or sequential treatment with other factors. Hematite (ferric oxide) and anatase (a titanium dioxide polymorph), when mixed with quartz particles, strongly inhibited the toxicity and transforming activity of quartz. The F600 quartz sample was analyzed and found to contain <2% kaolinite as impurity; it showed low toxicity, but a level of transforming activity comparable to quartz samples without this impurity. The peptide growth factor, tumor necrosis factor-alpha (TNF-alpha), was recently reported to act as a promoting agent following initiation by 3-methylcholanthrene (MCA) in BALB/3T3/A31-1-1 cells. In view of the previously reported role of TNF-alpha in silicosis, we studied, by two-stage experiments, whether TNF-alpha would act as a promoter in quartz-induced transformation in this cell line. The promoting activity of TNF-alpha was confirmed following MCA initiation (at 2 dose levels); in contrast, it was found (in two replicate experi- ments) that TNF-alpha inhibited quartz-induced transformation in this cell line. Heat-inactivated TNF-alpha was not inhibitory. The antioxidant dimethylsulphoxide (DMSO), given in the second stage, was found to inhibit quartz-induced transformation. Experiments are under way to determine if quartz has promoting activity and if quartz-induced transformation can be promoted by TPA or other agents.
