Abstract
Summary
A teratogenic dose of 14C-cyclophosphamide, an alkylating agent, was administered to pregnant mice to measure the alkylation of embryonic macromolecules as a function of time after treatment. Acid-soluble and acid-insoluble radioactivity was present in the maternal liver, placenta, and embryo during a 10-hr observation period after 14C-cyclophosphamide. The alkylation of macromolecules was demonstrated by the presence of radioactivity in the acid precipitate and nucleic acid and protein fractions of the tissues. The decline in specific activity of the nucleic-acid fraction after 14C-cyclophosphamide suggested that embryos had a poor ability, relative to the adult, to remove alkylated metabolite of 14C-cyclophosphamide from this fraction. These studies indicated that a teratogenic dose of 14C-cyclophosphamide produced alkylation of embryonic macromolecules and suggested that embryos differed from adults in their ability to repair macromolecules damaged by alkylating agents.
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