The influence of N-dialkyl and other cationic substituents on DNA intercalation and genotoxicity.

DNA intercalation by small chemical molecules can result in frameshift mutagenesis and chromosomal breakage. With evidence mounting that broadly diverse structures are capable of intercalating between DNA base pairs, it becomes important to better define those structural features that enhance intercalation strength and those that confer genotoxicity particularly among those intercalators that do not have the classical planar tricyclic fused ring structure. A chemical substituent that is present on many pharmaceutical and other biologically active molecules is the N-dialkyl group. In the present study, we investigate if and how the presence of an aromatic N-dialkyl or other cationic group affects the genotoxicity and DNA intercalation ability of 26 selected acridines, phenothiazines, benzophenones, triphenylethylenes and other classes of molecules. The data were obtained from the literature, from experiments using a cell-based DNA intercalation assay, and from modeling studies using a three-dimensional computational DNA docking program. It is demonstrated that cationic substitution can enhance both genotoxicity and electrostatic interactions within a chemical/DNA intercalation complex.

Can the oxytocin challenge test serve as the primary method for managing high-risk pregnancies?

The purpose of this investigation was to determine whether the oxytocin challenge test (OCT) could serve as the primary method for managing pregnancies characterized by possible placental insufficiency. One hundred and five patients underwent 225 oxytocin challenge tests; no perinatal deaths occurred. Eight tests were positive, 21 suspicious, and 196 negative. Because of data obtained in a preliminary study, all 8 fetuses with positive tests were delivered by cesarean section. Four of the 8 had repetitive suspicious tests prior to a positive test, suggesting that utero-placental function may deteriorate gradually. Urinary excretion of estriol did not decrease significantly in any patient, suggesting that the OCT is a more sensitive indicator of placental function than excretion of estriol. Except for patients with preeclampsia who were induced for maternal indications, all pregnancies with a negative OCT were allowed to terminate spontaneously. Five of the 97 fetuses with negative tests developed late-onset deceleration patterns during labor. This indicates that a negative OCT will not necessarily predict fetal tolerance to labor, contrary to assertions made by some other investigators. It is concluded that the OCT can serve as the primary method for assessing the fetal status in pregnancies characterized by placental insufficiency.