Reserpine-induced cell transformation without detectable genetic effects in Syrian hamster embryo cells in culture

Reserpine, a naturally occurring rauwolfia alkaloid, used mainly as an antihypertensive drug, was examined for its ability to induce cell transformation and genetic effects in Syrian hamster embryo (SHE) cells in culture. Treatment of SHE cells with 2 micrograms/ml of reserpine had no effect on cell growth, while 4 micrograms/ml of reserpine reduced the growth rate slightly and 8 micrograms/ml resulted in a significant inhibition of cell growth. Reserpine at doses of 4-8 micrograms/ml for 48 h induced a dose-related increase in morphological transformation of the cells. Reserpine-transformed colonies were morphologically indistinguishable from colonies transformed with benzo[a]pyrene (B[a]P) or other chemical carcinogens. Over the dose range that resulted in cell transformation, treatment of SHE cells with reserpine failed to induce any detectable gene mutations at two genetic loci, chromosomal abnormalities including structural and numerical changes, or DNA adduct formation. These findings indicate that reserpine may have carcinogenic potential by unknown mechanisms that do not include direct induction of gene and/or chromosome mutations.