Cocarcinogenic Activity of Bile Acids in the Chemical Transformation of C3H/10T1/2 Fibroblasts in vitro

Abstract

We have performed a series of experiments to determine directly whether bile acids influence carcinogenesis, using a C3H/10T1/2 cell transformation system in vitro. Treatment of the cells with the carcinogen, 3-methylcholanthrene (MCA), followed by the addition of lithocholic acid (LCA), produced a marked increase in the number of transformed foci a compared to the number induced by MCA alone. Simultaneous treatment with MCA and bile acid did not increase the number of transformed foci except in the case of MCA in combination with LCA. When cultured cells were exposed to MCA soon after removal of cholic acid or LCA, a statistically significant increase in the number of transformed foci was noted. When cultured cells were replated after continuous exposure to test compounds and then treated with MCA, no enhancement of the rate of formation of transformed colonies was observed. From these results, it appears that bile acids act as not only promoting but also as co-carcinogenic agents under certain circumstances.