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Biomedical subjects

M R Berger

Publications and source records attributed to M R Berger.

At least 109 records · Page 6Linked to original sources
PubMed1987

Therapeutic activity of ET-18-OCH3 and hexadecylphosphocholine against mammary tumors in BD-VI rats.

The present therapy experiments with two different transplantable mammary tumors were performed to compare the therapeutic efficacy in BD-VI rats of 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine (ET-18-OCH3) and hexadecylphosphocholine (HPC). Both compounds were administered orally, subcutaneously or intracutaneously at equimolar doses ranging from 4.8 to 88 mumol/kg/day five times per week for two weeks. Under the experimental conditions, both transplanted mammary carcinomas were moderately sensitive to the therapy with either HPC or ET-18-OCH3. Comparing both tumors, TMA2 was more sensitive than TMA1. The activity and toxicity of both compounds were dose-related in both tumor lines. Females seemed to be less sensitive with respect to antineoplastic activity and toxicity. Like ET-18-OCH3, HPC was active also at low, probably noncytotoxic doses associated with no detectable toxicity according to body weight development. This suggests that there are at least two different mechanisms of action that lead to tumor growth inhibition.

Administration, Oral↗
PubMed1987

Alkyl phosphocholines: toxicity and anticancer properties.

The study reports on the investigation of acute and subacute toxicity and on antineoplastic activity of hexadecylphosphocholine (HPC), the first compound of a new class of antineoplastic chemotherapeutics. In rats, the LD50 of HPC was 606 mumol/kg; the maximum tolerable dose over four weeks was 39 mumol/kg. Symptoms of toxicity were enteritis, spider cell activation in the liver, hemosiderosis in the spleen and reversible transaminase increase. The best therapeutic effect was observed on methylnitrosourea (MNU)-induced mammary carcinoma in the rat. Two transplantable mammary carcinomas in the rat and autochthonous benzo(a)pyrene-induced sarcomas exhibited low-grade sensitivity to HPC. The MXT mammary carcinoma of the mouse, the Walker 256 carcinosarcoma of the rat, and autochthonous acetoxymethylmethylnitrosamine-induced colonic tumors of the rat were not chemosensitive to HPC.

Animals↗
PubMed1987

Modulation of chemical carcinogenesis in rats by alkyl lysophospholipids.

The influence of 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine (ET-18-OCH3) and 1-hexadecylmercapto-2-methoxymethyl-rac-propyl-3-phosphocholine (TLP, BM41.440) on methylnitrosourea (MNU)-induced rat mammary carcinomas and of ET-18-OCH3 on 7,12-dimethylbenzanthracene (DMBA)-induced leukemias was investigated. Both agents effectively delayed MNU-induced mammary tumor formation at high, cytotoxic dosages but TLP had no influence at low "immunomodulatory" doses. ET-18-OCH3 also significantly protected against leukemia development in DMBA-treated Long-Evans rats.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1987

Paradoxical effect of dichlorobis(1-phenylbutane-1,3-dionato)molybdenum (IV), (Mo(bzac)2Cl2 on the growth of autochthonous chemically induced colorectal tumors in SD rats.

The influence of dichlorobis(1-phenylbutane-1,3-dionato)molybdenum (IV), (Mo(bzac)2Cl2) in acetoxymethyl-methylnitrosamine (AMMN) induced colorectal cancer in SD rats was assessed. Treatment was given intravenously twice a week for 10 weeks immediately after the end of the induction period (G1 and G2) or following coloscopic diagnosis of the tumors (G4, G5 and G6). Paradoxical therapeutic effect of Mo(bzac)2Cl2 on the growth the AMMN induced colorectal cancer was observed.

Animals↗
PubMed1987

Lack of therapeutic activity of the lipoidal amine CP-46,665 in rodent tumors and human non-seminomatous germ cell tumors growing in nude mice.

The alkyl-linked lipoidal amine 4-aminomethyl-1-[2,3-(di-n-decyloxy)-n-propyl]-4-phenylpiperidine (CP-46,665) was tested for therapeutic activity in 2 rodent tumor models and 2 human non-seminomatous germ cell tumors growing in nude mice. CP-46,665 failed to show therapeutic efficacy in 3-Lewis lung carcinoma (3-LL) growing in syngeneic C57Bl6-mice, in methylnitrosourea (MNU)-induced rat mammary carcinomas and in 2 human non-seminomatous germ cell tumor cell lines (H 12.1, H 12.7) growing in nu/nu NMRI-mice when given in a dose range including non-toxic doses and doses higher than the lethal dose for 10% of the treated animals (LD10).

Animals↗
PubMed1987

Locoregional application of 5-fluorouracil to the liver: alteration of pharmacokinetics and bone marrow toxicity in rats with thioacetamide-induced cirrhosis.

Pharmacokinetics and toxicity of 5-fluorouracil (5-FU) applied intra-arterially into the liver were studied in control and cirrhotic rats. Cirrhosis was induced by administering thioacetamide (4.5 mg/rat X day) over 6 months. 5-FU was administered into the hepatic artery at 30 mg/kg b.w. by bolus injection followed by infusion of 0.63 mg/kg X min for 40 min. Pharmacokinetics of 5-FU in plasma was studied by HPLC analysis. 5-FU induced toxicity was examined in a second group of control and cirrhotic rats at 48 and 168 hours after treatment with 5-FU (31.4 mg/kg b.w.) infused into the liver artery for 1 h. Analysis of toxicity was carried out by determining liver enzymes in plasma, bone marrow cellularity and colony forming units in vitro (CFU-C) and in vivo (CFU-S). The results indicate that during the period investigated (85 min) 5-FU was not eliminated from the plasma of cirrhotic rats in contrast to controls. The constant level of 5-FU in the plasma of cirrhotic rats induced a considerably higher myelosuppression in these animals, than the short-lived 5-FU peak in controls.

Alanine Transaminase↗
PubMed1987

Effects of vitamin A and E supplementation to diets containing two different fat levels on methylnitrosourea-induced mammary carcinogenesis in female SD-rats.

The aim of this study was to elucidate the effects of dietary vitamin A and E supplementation on tumorigenesis in correlation to the fat content of the respective diet in an animal model. One hundred and twenty female SD rats were initiated intravenously with 25 mg MNU kg-1 on day 50 of life. For a period of 6 months, beginning after the day of initiation, all animals received a semisynthetic diet containing 25% or 45% of the energy as fat, supplemented either with a 10-fold higher amount of naturally occurring vitamins A and E than in rat standard diets or, with a normal level of these vitamins. The experiment showed: (1) Vitamin A and E supplementation showed no significant chemopreventive effect against mammary tumour development. (2) This result was independent from the supplied fat level of the respective diet. (3) The fat content per se did not significantly influence mammary tumorigenesis.

Animals↗
PubMed1987

Influence of perinatal nicotine administration on transplacental carcinogenesis in Sprague Dawley rats by N-methylnitrosourea.

The administration of nicotine during the perinatal stages of life resulted in a significant decrease in tumours occurring after transplacental induction by N-methylnitrosourea (MNU). The overall tumour incidence following p.o. application of MNU to dams was 85% in rats of the F1-generation, the main occurrence being related to the neurogenic system (62% of the animals). Regular injections of nicotine before or after birth resulted in a reduction of malignancies by 17% and 22% (P = 0.08 and 0.0015), respectively. The difference in the incidence of neurogenic tumours proved to be highly significant (P less than 0.002) in rats of either sex, when nicotine was applied over 26 weeks following birth. There was a gender-specific imbalance in rats which received the carcinogen only, in favour of a lower tumour yield in females (P less than 0.04), which became less apparent when nicotine was given additionally. These findings suggest that nicotine is capable of modulating the expression of chemically induced tumours of the neurogenic system in a favourable way.

Animals↗
PubMed1987

The influence of different levels of dietary fat on the incidence and growth of MNU-induced mammary carcinoma in rats.

This study describes the influence of isocalorically fed diets (containing different amounts of fat) on tumor incidence and parameters of fat metabolism in female Sprague-Dawley rats. Comparisons are made between rats induced with methylnitrosourea (25 mg/kg body wt) and untreated controls (Group I). The animals received either control diets (3.9% fat by weight, Groups I and II) or fat-enriched diets (10.7%, Group III; 15.6%, Group IV; 21.4%, Group V) over a period of 180 days. At the termination of the experiment, intake of the diet containing 10.7% fat by weight (24% fat per total calories) was associated with the highest tumor incidence. Comparing the different diets, liver lipid concentrations in the individual groups increased with increasing dietary fat, whereas the total lipid in plasma decreased. During the feeding period, total lipid of the liver and plasma, and plasma cholesterol, increased in all groups, but triglycerides of plasma decreased. However, when plasma cholesterol and triglycerides were calculated as a relative amount of total lipid in plasma, cholesterol was found to be significantly decreased in Groups III and IV, and triglycerides were increased in Group III but decreased significantly in Groups I, II, and V at the end of the experiment.

Animals↗
PubMed1987

Combination experiments with very low doses of three genotoxic N-nitrosamines with similar organotropic carcinogenicity in rats.

The study was designed to assess the syncarcinogenic activity of very low doses of N-nitrosodiethylamine (NDEA), N-nitrosopyrrolidine (NPYR) and N-nitrosodiethanolamine (NDElA) in the liver of 1800 male Sprague-Dawley rats. The N-nitrosamines were administered throughout the rats' lives individually and in combination at three logarithmically spaced dose levels contained in drinking water. The dose levels in the individual dose-response experiments ranged from the lowest concentrations of previous experiments (NDEA, 0.1 mg/kg; NPYR, 0.4 mg/kg; NDElA, 2.0 mg/kg) to dosages 10 times lower and comprised a high, medium and low dose (escalation factor: 3.16). The high dose of the combination contained the three nitrosamine concentrations used as the medium doses of the individual nitrosamines. The medium combination dose resulted from the combined administration of the three lowest dosages, and the low combination dose consisted of three nitrosamine dosages which amounted to one-third of the low dosages respectively. Administration of these dosages was associated with a dose-dependent incidence of liver cancer: NDEA induced 45, 3.8 and 2.5%; NPYR caused 21.3, 5 and 1.3%; NDElA generated 7.5, 1.3 and 2.5%; and the combinations induced 16, 4.2 and 1.7% respectively. Untreated controls showed 0.6% liver cancer incidence. Besides the liver, the gastrointestinal tract, the neurogenic tissue, the urinary tract and the hematopoietic and lymphatic tissue were affected by tumor incidences increased over that of controls. There was, however, no well-defined dose dependency as with the liver tumors. These results indicate dose dependency of liver tumor formation even at very low exposure levels of the individual agents. The carcinogenic effects of the hepatotropic N-nitrosamines summed up in combination. The observed additivity was linear. Dose levels, which alone would presumably not have been carcinogenic, effected a significant cancer risk in combination.

Animals↗
PubMed1987

Syncarcinogenesis at low exposure levels of three nitrosamines with a common target of carcinogenic action: preliminary results.

The carcinogenic activities of N-nitrosodiethylamine (NDEA), N-nitrosopyrrolidine (NPYR) and N-nitrosodiethanolamine (NDELA) and of the combination of the three nitrosamines was determined in Sprague-Dawley rats at three logarithmically spaced exposure levels. The highest doses of the individual nitrosamines and of their combination, chosen so as to induce low specific incidences of liver tumours following life-long administration, resulted in median survival times for all treated groups of more than 30 months. The macroscopically determined incidences of liver tumours were 1% in control rats, 45%, 4% and 4% following administration of NDEA, 14%, 3% and 1% following administration of NPYR, 6%, 5% and 1% following administration of NDELA and 12%, 4% and 3% following the combined administration of all three nitrosamines. These results indicate linear, additive carcinogenicity with respect to their common target organ in the dose range investigated.

Animals↗
PubMed1986

Comparative carcinogenicity of ring-halogenated 3-methyl-1-phenyltriazenes and their 3,3-dimethyl analogs at equimolar dose levels in male Sprague-Dawley rats.

The carcinogenic activity of 3-methyl-1-phenyltriazene and its four 4- and 2-ring halogenated derivatives was similar to the previously reported carcinogenicity of the corresponding 3,3-dimethyl-1-phenyltriazene analogs tested at equimolar dose levels in adult male Sprague-Dawley rats. The strongest carcinogens in each series were 3-methyl-1-phenyltriazene and 3,3-dimethyl-1-phenyltriazene, respectively. The carcinogenic potency of the individual test compounds decreased with progressive 4- and 2-halogenation of the phenyl ring. The administration of either 3-methyl-1-(2,4,6-trichlorophenyl)- or 3-methyl-1-(2,4,6-tribromophenyl)-triazene gave a negligible tumor yield not different from that observed in the control animals. Moreover, 3,5-dichloro-2-(3,3-dimethyl-1-triazeno)-benzoic acid or its ethyl ester, were found to be strong carcinogens that exclusively induced kidney tumors.

Animals↗
PubMed1986

Experiments on the efficacy and toxicity of locoregional chemotherapy of liver tumors with 5-fluoro-2'-deoxyuridine (FUDR) and 5-fluorouracil (5-FU) in an animal model.

For the investigation of locoregional chemotherapy of liver neoplasms we developed a standardized animal model in the rat. Continuous infusion therapy or repeated bolus injections of FUDR or 5-FU were given via the hepatic artery, the portal vein or the vena cava in tumor-bearing animals. The efficacy of the treatment was determined by measuring the tumor volume 3 weeks after tumor cell implantation. For the evaluation of the local and systemic toxicity serum GOT, GPT, and total bilirubin were determined. DNA single strand breaks were assessed in isolated liver and bone marrow cells. Inhibition of colony formation of bone marrow stem cells was determined by CFU-C and CFU-S bioassay. A significant reduction of tumor growth was observed only after continuous infusion of FUDR via the hepatic artery. Systemic toxicity was lowest in this group for both compounds while the local liver toxicity was only slightly elevated.

Animals↗