Effect of a Folic Acid Antagonist, Aminopterin, on Fetal Development and Nucleic Acid Metabolism in the Rat

Abstract

When a single dose of aminopterin was injected into rats on the tenth day of pregnancy, the embryos were destroyed and completely resorbed if the level of dosage was 200 µg or above. Step-by-step reduction of the analogue permitted more of the fetuses to survive and these showed a low number of congenital defects. Fetal liver DNA in these young was depressed at the higher levels of dosage but RNA was unaffected. When folic acid was administered at varying levels one hour prior to an injection of 150 µg aminopterin, the effect of the aminopterin was partially reversed. There was a statistically significant enhancement of the DNA and of the RNA synthesis when the lower levels of folic acid were used. However, at the highest level of folic acid, the DNA and RNA synthesis in this group were both depressed. When folic acid was given alone, the DNA was again significantly depressed at the highest level of dosage but RNA was unaffected. At this higher level of folic acid some abnormal young were found. Thymidine alone or in combination with inosine was unsuccessful in reversing the aminopterin effect.