Cytogenetic studies two N-substituted Cytoxan derivatives on human leukocytes in vitro. I. Dose-effect-levels

Abstract

Unlike cyclophosphamide (Endoxan®, Cytoxan®) N, N, N′-tris-(2-chloroethyl)-N′,O-propylene phosphoric acid ester diamide and N-(2-chloroethyl)-N′-(2-chloroethyl)-N′,-O-propylene phosphoric acid ester diamide induced chromosomal aberrations in human leukocytes in vitro. The majority of these lesions consisted of chromatid breaks, acentric fragments, and isochromatid breaks. Infrequently interchanges and ring chromosomes were observed. The percentage of metaphases with chromosomal damage increased exponentially, the mean breakage frequency per metaphase, however, rose approximately linearly with the applied concentration. A possible cleavage of the nitrogen-phosphorus bond and the breakdown of the inactive cyclic forms of the two investigated compounds in vitro is discussed.