QUANTITATIVE STUDIES ON CONCURRENT FACTORS IN NEOPLASTIC TRANSFORMATION

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Studies were continued on mechanisms of transformation in the mouse embryo cell line, BALB/3T3 clone A31-1-1. Transformation was obtained with several metals. Studies with trivalent and pentavalent arsenic (As) showed that trivalent As was four times more active than pentavalent As. However, when correlated with the calculated As uptake and cell burden, toxicity and transformation frequency were found to be the same for both forms of As. The results of metabolic studies indicate that trivalent As is the form responsible for the toxic and transforming effects, independently of the valence state of the As exposure. BALB/3T3 cells transformed by metals and by organic carcinogens, or spontaneously, when inoculated in nude mice were found to be tumorigenic but not metastasizing, even by intravenous administration. This finding is consistent with the lack of type IV collagenolytic activity observed in these transformed cell lines. Induction of metastatic activity by further treatment with the ras oncogene or with carcinogens is under investigation.