The effects of the nicotinamide sensitive teratogen 3-acetylpyridine on chick limb mesodermal cells in culture: biochemical parameters.

3-acetylpyridine (3AP) causes severe muscular hypoplasia in vivo and seems to potentiate chondrogenic expression of limb bud cells in vitro. In both cases nicotinamide completely relieves these effects. In cell cultures, 3AP causes a substantial drop in nicotinamide incorporation. This decreased incorporation represents not only decreased cellular pools of nicotinamide but also decreased DPN-TPN pools. 3AP also decreases the rate of RNA, protein, and mucopolysaccharide synthesis. 3AP does not affect the rate of DNA synthesis which is constantly decreasing as chondrogenic expression increases. Even though the rates of macromolecular synthesis seem to be reduced, the specific activity of an obligatory enzyme for mucopolysaccharide assembly, UDP glucose pyrophosphorylase, dramatically increases with 3AP-treatment. This is interpreted to mean that 3AP potentiates of cartilage synthesizing machinery which is observed as a potentiation of chondrogenic expression. These data are discussed with regard to nicotinamide's proposed role in affecting the development of chick limb mesodermal cells into muscle and cartilage producing phenotypes. It is proposed that alterations in local concentrations of essential molecules like nicotinamide, DPN, or TPN can control phenotypic expression.