Gerd Reznik

Inhibition of protein-kinase-C--dependent cell proliferation of human lung cancer cell lines by the dihydropyridine dexniguldipine.

The dihydropyridine, dexniguldipine hydrochloride (B859-35), has shown therapeutic activity in experimentally induced neuroendocrine hamster lung tumors and demonstrated antiproliferative effects in a mammary cancer cell line via inhibition of Ca2+ calmodulin. Studies in NIH 3T3 fibroblasts have provided evidence that dexniguldipine may also inhibit protein kinase C (PCK). In this study, we have tested the hypothesis that dexniguldipine may inhibit the proliferation of lung cancer cells in response to autocrine or exogenous activation of PKC. Using a panel of human lung cancer cell lines, we show that dexniguldipine is a potent inhibitor of mitogenic signal transduction pathways dependent on PKC activation in several small-cell and non-small-cell lung cancer cell lines while it failed to inhibit cyclic-AMP-dependent cell proliferation.

Investigations on the carcinogenic burden by air pollution in man. Intratracheal instillation studies with benzo(a)pyrene in bovine serum albumin in Syrian hamsters.

The chronic effect of benzo(a)pyrene (B(a)P) administered intratracheally in bovine serum albumin was studied in Syrian golden hamsters. Dose levels of 0.1 mg, 0.33 mg and 1.0 mg of B(a)P induced papillomas and carcinomas of the trachea, stem bronchi and bronchioles. In addition to such tumours, the mucosa of the respiratory tract revealed a variety of atypical epithelial alterations. Although survival time exhibited a dose-dependency, tumour incidence did not. The incidence of respiratory tract tumours was higher in female hamsters than in males. The results of these investigations are statistically evaluated.

Differences in blood values depending on age in laboratory-bred european hamsters (Cricetus cricetus L.):

No significant differences in blood parameters were found between males and females aged 13-900 days. A comparison of the various age groups showed significant differences in the number of erythrocytes, leucocytes, thrombocytes and in the diameter of red blood cells. The number of erythrocytes and leucocytes was lowest, and the erythrocytes had the largest diameters in young animals. The number of thrombocytes was lowest in older animals.

Ganglioneuroma, Adrenal, Rat

The size of the neoplasms vary but are often as much as 10 mm in diameter (Fig. 28) and displace much of the affected adrenal. In all cases from the literature, only one adrenal was involved. Although the affected adrenal is enlarged, some magnification is required to determine the nature of the enlargement.

Induction of renal pelvic tumours in sprague-dawley rats by di-isopropanolnitrosamine

Transitional cell papillomas and carcinomas of the renal pelvis were observed in Sprague-Dawley rats after subcutaneous (s.c.) treatment with di-isopropranolnitrosamine (DIPN). These tumours occurred unilaterally and appeared as early as 24 weeks after the commencement of treatment. The tumours frequently filled the entire renal pelvis and compressed the kidney parenchyma. The malignant neoplasms demonstrated infiltrative growth into the adjacent medullary parenchyma.

Carcinogenic effects of different nitroso-compounds in Chinese hamsters. II. N-nitrosomorpholine and N-nitrosopiperidine.

A total of 320 Chinese hamsters (Cricetulus griseus) (CH) were subcutaneously (s. c.) treated with 1/5, 1/10, or 1/20 LD50 of N-nitrosomorpholine (NM) or N-nitrosopiperidine (NP). In the CH, NM and NP both produced up to a 100% rate of papillomas of the cheek pouch, tongue, pharynx, esophagus and forestomach. Occasionally squamous cell carcinomas also developed in these organs. A high rate of hepatomas was realized by NP. 320 Chinesische Zwerghamster (Cricetulus griseus) (CH) erhielten subcutan 1/5, 1/10 oder 1/20 der LD50 N-Nitrosomorpholin (NM) oder N-Nitrosopiperidin (NP). Beide Substanzen führten zu Papillomen in 3 Backentaschen, Zunge, Pharynx, Oesophagus und Vormagen. In einigen Fällen fanden sich darüber hinaus in den Organen auch Plattenepithelcarcinome. Weiterhin wurde nach Behandlung mit NP eine hohe Hepatomrate beobachtet.

Inhalation experiments with 14C-labelled cigarette smoke II. The distribution of cigarette smoke particles in the hamster respiratory tract after exposure in two different smoking systems

Male and female Syrian golden hamsters were exposed to the smoke of [14C]dotriacontane-16,17 ([14C]DOT)-labelled cigarettes in 2 different exposure systems. These 2 systems differed in terms of the smoke concentration drawn into the exposure chamber. To compare the effectiveness of the exposure systems, the inhaled dose of 14C-labelled cigarette smoke was determined in the different parts of the hamster respiratory tract by liquid scintillation counting. About 6 times more smoke particles were deposited in the respiratory tract after exposure to high smoke concentration with intermittent puffs of fresh air (closed system) than after exposure to smoke diluted with air (open system). About 80% of the diluted smoke reached the bronchi and lung compared to approximately 60% of the concentrated smoke. The remainder of the dose was trapped in the upper respiratory tract, mainly by the nose and larynx. Additionally, in the open system the total dose of inhaled smoke was dependent upon the position in the exposure chamber. The results are discussed with respect to the use of the exposure systems for chronic cigarette smoke inhalation studies in experimental respiratory tract carcinogenesis.

Lung tumors induced by chronic inhalation of 1,2-dibromo-3-chloropropane in B6C3F1 mice☆

1,2-Dibromo-3-chloropropane (DBCP) was inhaled by B6C3F1 mice of each sex at concentrations of 0.6 or 3.0 ppm for 6 h/day, 5 days/week, for 103 weeks. Untreated controls consisted of 50 mice of each sex. All surviving animals were killed at 104 weeks. Survival in the high-dose groups of female mice was significantly shorter than that in the corresponding controls. Alveolar-bronchiolar adenomas or carcinomas occurred in both male and female mice with dose-related trends (P < 0.007) in males and (P < 0.002) in females. Papillary carcinomas in the lung occurred in low-dose female mice at an increased incidence compared with controls (P < 0.006). Many induced tumors were morphologically different than those in controls.

Inhalation experiments with 14C-labelled cigarette smoke. I. Determination of the effectiveness of two different smoking systems with labelled cigarettes.

Two different smoking systems were tested by exposing Syrian golden hamsters to the smoke of cigarettes labelled with (14C)dotriacontane-16, 17 (DOT). In 3 experiments, the activity of mainstream and sidestream Total Oarticulate Matter (TPM) and of butts and ash was determined. Comparing the results, the system involving individual exposure was shown to provide the animals with higher amounts of mainstream TPM than the system using simultaneous exposure of numerous animals.

Carcinogenic effects of different nitroso-compounds in chinese hamsters: N-dibutylnitrosamine and N-nitrosomethylurea

Three hundred and twenty Chinese hamsters (Cricetulus griseus) (CH) were subcutaneously (s.c.) treated with 1/5, 1/10 or 1/20 the mean lethal dose (LD50) of N-dibutylnitrosamine (DBN) or N-nitrosomethylurea (NMU). In several respects these two substances produced the same organotropy in the CH as in the Syrian golden (SGH) and European hamsters (EH). DBN prolonged lung tumours and neoplasms of the injection site. NMU induced tumours of the injection site only.