Morphological changes induced by picolinic acid in cultured mammalian cells.

The morphological changes induced by picolinic acid treatment in cultured normal rat kidney (NRK) and BALB/3T3 cells, and SV40-transformed NRK and BALB/3T3 cells were accompanied by altered distribution of cytoskeletal elements. These changes were prevented by the divalent cation ionophore A-23187. Untreated transformed cells were predominately round or fusiform in shape while untreated normal cells were predominately flat; both normal and transformed cells contained relatively few microfilaments and microtubules. Culturing these cells in medium containing 3 mM picolinic acid induced microfilaments and microtubules to accumulate in bundles at the cell periphery. In transformed cells the agent also induced the formation of long narrow cytoplasmic processes which showed parallel arrays of microfilaments near the cortex and microtubules near the center. These changes were apparent within 8 to 12 hr and acquired maximal expression by 24 to 36 hr. Picolinic acid also enhanced the formation of substrate adhesion plaques and intercellular adherens junctions in transformed cells. In SV40-transformed cells but not in normal cells mitochondria showed characteristic toxic alterations. Most of the mitochondria were electron dense and elongated or showed enlargement, swelling or vacuolated areas after 48 hr of treatment. The mitochondrial changes clearly reflected a selective toxicity induced by picolinic acid in SV40-transformed cells. These results suggest that picolinic acid specifically interferes with systems that are important in the determination of cell shape and neutralizes some of the effects of transformation.