Biosynthesis of deoxyribonucleic acid, ribonucleic acid and protein in vivo by neonatal mice after a toxic dose of cyclophosphamide

Abstract

Swiss-Webster mice received 80 mg kg of cyclophosphamide 1 day after birth and were allowed to develop or were given 100 μCi kg of [ 14C]labeled thymidine, uridine or leucine at various times afterwards. Growth retardation and increased mortality were noted during the postnatal period. DNA synthesis, as measured by [ 14C]thymidine incorporation, was inhibited in the liver, brain and carcass for at least 3 days after cyclophosphamide treatment. DNA synthesis was reduced 1 day after treatment to 8.4, 26 and 25 per cent of control in the liver, brain and carcass respectively. RNA synthesis, as measured by [ 14C]uridine incorporation, was reduced only in the liver and brain. Liver RNA synthesis was reduced to 36 and 64 per cent of control at 1 and 5 days after cyclophosphamide treatment respectively. Brain RNA synthesis was reduced to 78 and 64 per cent of control 1 and 4 days after treatment. [ 14C]leucine incorporation, taken as a measure of protein synthesis, was not affected in a manner which would indicate that drug treatment altered this parameter of differentiation. The data suggested that cyclophosphamide neonatal toxicity may be related to a prolonged inhibition of DNA and RNA synthesis during the first 5 days of life. This observation was correlated with the slow rate of cyclophosphamide activation and excretion in neonatal mice.