Abstract
To elucidate the mechanism of sulfonamide-induced malformations in mice, the effects of PABA, folic acid, tetrahydrofolic acid, nicotinamide, pyridoxine, 1-acorbic acid and riboflavin on the teratogenic action of sulfadimethoxine, manifested mainly as cleft palate, were studied. Tetrahydrofolic acid, an active form of the folic acid, was found to block teratogenicity completely. Nicotinamide, pyridoxine or 1-ascorbic acid reduced induction of the malformed embryos, while PABA, folic acid and riboflavin had no effect. As for the process through which such inhibiting effects are achieved, it isconsidered that co-factor-related or metabolism-promoting factors such as tetrahydrofolic acid, nicotinamide, pyridoxine or 1-ascorbic acid activate the metabolism around the tetrahydrofolic acid in a folate metabolism. It may be concluded that the teratogenic effect of sulfadimethoxine is not caused by the deficiency of folic acid due to its competitive antagonism with PABA which is known as the substantial step of its antibacterial action. Rather, it is the interference with the folate metabolism around the tetrahydrofolic acid in early embryos characterized by vigorous protein synthesis which is suggested to be the cause.
