Diaplacental carcinogenesis: Tumor localization and tumor incidence in NMRI mice after diaplacental initiation with DMBA and urethane and postnatal promotion with the phorbol ester TPA in a modified 2-stage Berenblum/Mottram experiment

Summary Diaplacental initiation with the carcinogens DMBA or urethane followed by repeated topical treatment of mice of the F₁ generation with the tumor promoter TPA leads to the formation of benign and malignant tumors on the skin of the back as well as in other tissues and organs. The tumor yield in this modified 2-stage Berenblum/Mottram experiment considerably exceeds the number of spontaneously formed tumors and of tumors produced by initiation alone. Further differences can be demonstrated in the malignancy rate, the formation of multiple tumors in various organs, additional non-neoplastic alterations and in a reduction of the lifetime of the animals. The effect of the tumor promoter TPA is not restricted to carcinogenesis in the back skin. Obviously, TPA is able to activate inititated tumor cells in internal organs to form tumors. This, in turn, implies the absorption of the substance via the blood vessels and its distribution throughout the body. The preferential occurrence of tumors in the genital tract of female mice (carcinomas and sarcomas of the vaginal wall, granulosa cell tumors of the ovaries) points to a possible hormonal involvement; in this context, relevance to prenatally induced tumors in human pathology is discussed. The results emphasize the important role of prenatal carcinogenesis and indicate the increased risk to man by either prenatal initiation or postnatal promotion.     

Influence of various cationic amphiphilic drugs on the phase-transition temperature of phosphatidylcholine liposomes

The influence of 16 cationic amphiphilic compounds from various pharmacological groups on the phase-transition temperature (T_t) of dipalmitoyl-phosphatidylcholine (DPPC) liposomes was investigated using the method of differential scanning calorimetry. All drugs, the hydrophobicity of which varied in a wide range, depressed T_t. Biphasic dose-effect curves were obtained when the reduction of T_t (ΔT_t) was plotted vs the molar ratio of drug/DPPC; beyond a plateau, T_t could again be reduced markedly by increasing the molar ratio. Concomitantly with the depression of T_t, the width of the transition peak changed in a characteristic way: it broadened during the (first) steep part of the dose-effect curves and became narrow like a control transition when the plateau of the dose-effect curves was reached. At still higher ratios the peak broadened again and eventually vanished, probably due to a detergent-like effect of the drug. Increasing hydrophobicity of the compounds shifted the dose-effect curves to lower molar ratios and enhanced the ΔT_t, attained at the plateau phase. It is proposed that the different potencies of the drugs to depress T_t result from different binding equilibria between the compounds and DPPC membranes, the individual equilibrium being determined by hydrophobia attraction and electrostatic repulsion.     

UV versus chemical polymerization of glycol methacrylate (GMA) in enzyme histochemistry.

The influence of the mode of polymerization of GMA on the enzyme activities of differently fixed rat livers was studied. It was found that with increasing time of UV-polymerization several enzyme activities were inhibited whereas chemical polymerization was comparatively less harmful. The histochemical reactivity of substrates such as glycogen was not impaired by the mode of polymerization, which is in contrast to the increased basophilia of DNA and RNA after UV-polymerization.     

Fluorometric determination of the quality of FITC-anti influenza conjugates (author's transl)]

A fluorometric method for the evaluation of FITC-anti influenza conjugates is described. The titre and that dilution required for the complete detection of antigens can be determined. It is possible to verify the probability of detection in per cent for any dilution stage and to compare objectively different batches. For this microtest only 0,2 ml conjugate are necessary.     

Dopamine and norepinephrine depletion in ring doves fed DDE, dieldrin, and Aroclor 1254

The levels of dopamine and norepinephrine were measured in one-half of the brain of ring doves fed a control diet or a diet containing 2, 20, or 200 ppm DDE; 1, 4, or 16 ppm dieldrin; or 1, 10, or 100 ppm Aroclor 1254. Levels of DDE, dieldrin, or Aroclor 1254 were determined in the other half of each brain. The intermediate and high levels of each chemical caused depletions in both neurotransmitters, and brain residues of each chemical were negatively correlated with levels of neurotransmitters. The highest concentrations of DDE, dieldrin, and Aroclor 1254 depressed averages of dopamine to 42.4, 41.4, and 45.2% of the control level and norepinephrine to 61.6, 62.0, and 56.9% of controls, respectively. Depletions of dopamine and norepinephrine could result in abnormal behavior of contaminated birds in the wild, and the detection of such depletions could become an important tool in assessing contaminant-induced behavioral aberrations in birds.     

Uptake of 11C-l-and d-methionine in brain tumors

¹¹C-labeled l-and d-methionine uptake was measured in seven patients with brain tumors using positron emission tomography. Tumors accumulated both isomers of the tracer. The strongest uptake occurred in tumors with a high grade of malignancy, while low grade tumors accumulated less activity. The l to d uptake ratio in tumor regions ranged from 0.92–1.25. Conventional ^99mTc-DTPA scans revealed blood-brain barrier damage in two patients with no or only slight ¹¹C-methionine accumulation, while one patient with a negative ^99mTc-DTPA scan accumulated ¹¹C-methionine in the tumor region. In view of the biochemical pathway of methionine and the present findings, it is concluded that the uptake reflects metabolic activity in brain tissue rather than uptake by diffusion due to disruption of the blood-brain barrier.     

Intra-arterial digital subtraction angiography of the spinal cord

Digital subtraction angiography (DSA) of the spinal cord was performed in 6 patients using selective intra-arterial injections of contrast material. Two arteriovenous malformations of the spinal cord, 1 dural fistula, and 1 case of multiple hemangioblastomas were studied. Contrast and spatial resolution were satisfactory for defining normal and abnormal vascularity while reducing examination time, contrast dosage, patient discomfort, and film cost. The only significant limitation was misregistration artifacts seen on lateral views encompassing the diaphragm.     

Embryotoxic effects of thalidomide derivatives on the non-human primateCallithrix jacchus

The teratogenic potencies of the enantiomers of 2-(2,6-dioxopiperidine-3-yl)-phthalimidine (= EM 12), a teratogenic thalidomide analogue, were investigated inCallithrix jacchus, a primate very sensitive to the teratogenic action of this thalidomide analogue. The results indicate that the S-(–)-form of EM 12 is clearly more teratogenic than the R-(+)-form. The interpretation of the studies designed to evaluate stereo-selective differences in the teratogenicity of the enantiomers becomes difficult, since both enantiomers racemise in vivo with appreciable rates (Schmahl et al. 1988a, b). Therefore, it cannot be concluded as yet that the R-(+)-form lacks all teratogenic potential.Abbreviations EM 12 2-(2,6-dioxopiperidine-3-yl)-phthalimidine - S-EM 12 S-(–) enantiomer of EM 12 - R-EM 12 R-(+) enantiomer of EM 12     

Ultrathin crosslinked membranes at the interface between oil and water

The tensio-active properties of different types of diesters can be used to synthesize two-dimensional model networks at the interface between oil and water. We have systematically studied rubber-elastic, glass-like and transient membranes, which are stabilized and crosslinked by physical or chemical contacts. The kinetics of surface gelation and the mechanical properties of the crosslinked membranes were investigated by measuring two-dimensional rheological parameters, such as the shear modulus or the surface viscosity. The experimental data of these investigations are in fairly good agreement with the theoretical predictions of percolation theories. Further informations on the molecular structure of the crosslinked membranes can be obtained from electron spin resonance (ESR) measurements. Using spin labels of significantly different sizes, which are diffusing from the aqueous environment into the oil phase, it is possible to determine the average mesh size of the interfacial network structure. The systematic study of these ultrathin membranes offers new insights into aspects of current research, and opens interesting new technical applications.