Induction of a malignant phenotype in BALB/c 3T3 cells by 1,1,2,2-tetrachloroethane

BALB/c 3T3 cells transformed by 1,1,2,2-tetrachloroethane, the most toxic chloroethane, acquired a fully malignant phenotype. They were capable of growing in soft agar, were tumorigenic when injected in athymic mice and produced pulmonary nodules after i.v. injection. Untreated BALB/c 3T3 cells were weakly tumorigenic (3/9 animals developed tumors after a longer time) and induced rare pulmonary nodules in a low percentage of animals. Transformed cells were also invasive in the chemoinvasion assay. Moreover, they grew in a gel of reconstituted basement membrane (matrigel), penetrating the gel and assuming a branching morphology that has been associated to the malignant phenotype. By contrast, spontaneous transformants isolated from solvent controls were poorly invasive in these assays. These results show that 1,1,2,2-tetrachloroethane could play a role in the late steps of multistage carcinogenesis.