Influence of prenatal administration of busulfan on the postnatal development of mice. Production of a syndrome including hypoplasia of the thymus

Publisher Website
Google Scholar
Abstract
The alkylating agent busulfan (1,4‐butanediol dimethanesulfonate) was given to mice on day 1 to 18 of pregnancy, each animal receiving a single 30 mg/kg ip dose. Growth and mortality rates from birth to the end of the 8th week were observed in 510 young. Starting from the gestation day 9 treatment caused significant growth retardation in 51.2% of offspring. The frequency was highest when injections were given on day 10, 15, or 16. Treatment on day 9, 10, 15, 16, or 17 was associated with an overall death rate of 37.6%. There was a direct relation between retarded growth and premature death, and both occurred chiefly in animals treated during fetogenesis. In 23.8% of the young from females treated on day 10, 11, or 12 extreme stunting, wasting, abnormal hair, skeletal muscle weakness, and, in two cases, necrotic foci in the liver were associated with hypoplasia of the thymus; 30% of the animals died before the end of the 1st month. Damage of some or all the thymus cell precursor lines was probably the origin of the hypoplasia of this organ, which, in turn, was the likely cause of the other features of the syndrome. These results emphasize the need for studying postnatal development when testing embryopathic effects of drugs, and point to the possibility of using busulfan as an experimental model in the study of the thymus ontogenesis and development of immune responsiveness.