AC Concentrations Research Articles

Selectivity of N-[2-(Dimethylamino)ethyl]acridine-4-car☐amide towards Lewis lung carcinoma and human tumour cell lines in vitro

N-[2-(Dimethylamino)ethyl]acridine-4-car☐amide (AC; NSC 601316) is a chemically novel antitumour agent which is thought to interact with DNA topoisomerase II and which has DNA binding properties which are distinct from other acridine derivatives such as amsacrine and its disubstituted analogue CI-921. AC is one of the most active agents, experimental or clinical, against the Lewis lung carcinoma in mice. AC is the first acridine derivative in our hands to show higher activity against cultured Lewis lung cells than against leukaemia lines. AC is more active against two human leukaemia cell lines (U-937 and Jurkat) than against a melanoma line (MM-96) and is inactive against the HT-29 human colon line. With all cell lines tested, cytotoxicity was higher at AC concentrations of 3–6 μM than at 15–20 μM. AC at a concentration of 20 μM inhibited the cytotoxicity of amsacrine and CI-921, but not that of another topoisomerase-directed drug doxorubicin. A Lewis lung line which had been cultured for a long period was less sensitive than a line freshly isolated from mice, but sensitivity of the cultured line recovered after it was multiply passaged in vivo. Long-term cultures may therefore be less appropriate than short-term cultures for predicting effectiveness of AC in vivo.

In vitro human lymphocyte PHA response- the heterogeneous effect of methylazoxymethanol acetate.

In earlier studies on the effect of methylazoxymethanol acetate (MAM AC), a mutagen, teratogen and carcinogen, upon sister chromatid exchange, the concentrations tested in short-term lymphocyte cultures from 9 individuals were not identical for each person. (The concentrations were derived from dose-effect curves for each individual, involving the quantity of MAM AC [5...50...80 µg/ml] versus blast transformation using PHA.) The differences obtained between the curves were investigated further by repeating the dose-effect curves in cell cultures derived from 10 normal male individuals, except that Ficoll-Hypaque-purified mononuclear cells were cultured at a concentration of 3 × 10<sup>5</sup> viable cells/ml. Five identical microwell cultures (150 µl) were tested for each variable within an individual experiment. Controls with and without PHA (PHA+, PHA-) were included. The results show that not all individuals’ cultures exhibited the same PHA response for each concentration of MAM AC. In the 10 cases studied: (1) dose-effect curves were not uniform for all experiments; (2) the percentages of <sup>3</sup>H-incorporation at 5 µg/ml of MAM AC compared to that of PHA+ controls were not the same across experiments; depending on the experiment, 5 µg/ml significantly increased, reduced or had no effect on PHA when <sup>3</sup>H-uptake was compared to PHA+ control levels; (3) when mean log values of the above percentages were plotted with their confidence intervals, striking differences were exhibited between individuals or groups of individuals; (4) the TD<sub>50</sub> values, referred to as the concentration of MAM AC at which half as much label was incorporated as compared to PHA+ control cultures, were different, and (5) the lowest MAM AC concentrations effective in reducing <sup>3</sup>H-uptake levels to those of PHA-controls were not the same. Familial and/or laboratory animal studies will demonstrate whether these differences are genetically determined.

Synergistic action of n-dodecylamine withn-capric acid on the corrosion of steel in sulphuric acid solution

Studies were performed on the effect of mixtures of n-capric acid (Ac) with n-dodecylamine(Am) on the corrosion rate of mild steel in IN H 2SO 4 at 25°C. The concentration of Ac was changed within the range from 3·10 −5 to 1·5 10 −4 mole/1, and that of Am from 1·10 −5 to 2·10 −4 mole/1. The maximum increase in the inhibitive efficiency of Ac by additions of Am was observed at concentrations close to that of the saturated solution of Ac in 1N H 2SO 4. It was found that Ac and Am mixtures were adsorbed at the metal surface following the adsorption isotherm of Frumkin. This may be written: θ s 1 − θ s exp ⁡ f m i x θ s = K c A m c A c where θ 5—coverage degree by both substances, ƒ mix—parameter connected with changes of the adsorption energy with coverage, K—equilibrium constant of the adsorption reaction, c Am, c Ac—concentrations of Am and Ac respectively. The standard free energy of adsorption of the mixture of Ac with Am is approximately equal tothe sum of the standard free energies of adsorption of these compounds taken separately, and fin,: is the arithmetical mean of the respective single values. This suggests that the ratio of the number of Ac to Am molecules in the adsorbed layer is 1 : 1. Most probably, micellae having such a composition (AcAm) already exist within the sulphuric acid solution.