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Biomedical subjects

J H Koeman

Publications and source records attributed to J H Koeman.

71 records · Page 4Linked to original sources

Biological activity of technical Aroclor 1254 compared to Aroclor 1254 residues: swine fat residues fed to broiler cockerels.

Fat from Aroclor 1254-treated swine was rendered and incorporated into the diets of broiler chicks for 3-4 weeks. The technical Aroclor 1254 which was fed to the swine was also mixed into control lard for comparison at dietary concentrations of 0.07-9.0 mg/kg. The swine-residue PCB seemed to have a higher proportion of strong microsomal inducers, but the technical PCB was slightly more effective in inducing ethoxy resorufin and p-nitro-anisole (pNA) O-dealkylases than the swine-residue PCB. No overt signs of toxicosis were apparent and none of the diets resulted in changes in growth, relative organ weights, microsomal protein or high affinity pNA O-dealkylase. Increases in cytochrome(s) P-450 were significant only at the higher dietary concentrations (approx. 9 mg/kg) while ethoxyresorufin O-dealkylase was induced at dietary concentrations below 1 mg/kg.

Adipose Tissue↗

Environmental toxicology, its history and future with special attention to the situation in the Netherlands.

Large scale pollution of the environment by pesticides and other chemicals only started in the fifties and early sixties. Chlorinated hydrocarbon pesticides and methyl mercury compounds appeared to have a marked impact on the populations of many animal species, especially birds. It is recognized that prof. dr. H. van Genderen, who retired this month, made a most valuable contribution to the timely detection of these problems in the Netherlands. Environmental toxicologists engaged in studies to predict environmental hazards by chemicals require toxicological skill as well as insight into the structure and functioning of ecosystems.

Academies and Institutes↗

Effects of dieldrin, diet, and bedding on enzyme function and tumor incidence in livers of male CF-1 mice.

The effects of naturally occurring microsomal enzyme inducers on hepatocellular drug-metabolizing enzyme systems and also upon the incidence of "spontaneous" liver tumors in CF-1 mice were investigated, using animals maintained on semisynthetic diet and filter-paper bedding as controls. The administration of dieldrin, a potent microsomal enzyme inducer with tumorigenic properties in livers of CF-1 mice, to some of the experimental treatment groups served as a positive control. Conventional diet and sawdust bedding caused induction of the liver monooxygenase system, although this effect was far less pronounced than that produced by dieldrin. The incidence of liver tumors in mice exposed to conventional diet and sawdust bedding was similar to that seen in the control group. The incidence of liver tumors was significantly increased in dieldrin-treated mice, including those maintained on semisynthetic diet and filter-paper bedding. Both benign and malignant tumors were found in dieldrin-treated mice, the latter type of lesion showing evidence of lung metastasis. These results, together with evidence that dieldrin and its mammalian metabolites possess neither genotoxic activity nor potential, are consistent with the concept that dieldrin exacerbates or facilitates the expression of a preexisting oncogenic factor which is genetically linked and possibly viral in origin.

Animals↗

Mutagenic effect of dichloromethane on Salmonella typhimurium.

The possible mutagenicity of the organic solvent dichloromethane was investigated with the mutation test as described by Ames et al. The compound was mutagenic in both tester strains used, namely TA98 and TA100. The administration of rat-liver homogenate did not appear to be essential though it slightly increased the number of mutations.

Genetic Techniques↗

Cytogenetic changes in fish exposed to water of the river Rhine.

The induction of chromosome aberrations in fishes, exposed to Rhinewater, was investigated. The mudminnow, Umbra pygmaea, was chosen for this study, because of its ideal karyotype of 22 large chromosomes. Gill cells were used for chromosome studies. Fish, kept in Rhinewater for 11 days had chromosome breaks in approximately 30% of the metaphases studied. Control fish, exposed to a very good quality of untreated groundwater had breaks in about 8% of the metaphases. Several Rhinewater extracts were tested for their mutagenic potential in the Salmonella-microsome test. The fraction of aromatic compounds was found to be positive. This may indicate that one or more of the compounds present in this fraction were also responsible for the cytogenetic changes found in the fish.

Animals↗

Mercury and selenium in marine mammals and birds.

Information is provided concerning the concentrations of mercury and selenium in tissues of marine animals. In marine mammals a 1:1 Hg/Se molecular increment ratio was found and an almost perfect linear correlation between mercury and selenium. It is suggested that marine mammals are able to detoxify methylmercury by a specific chemical mechanism in which selenium is involved. The results also indicate that the fate of methylmercury in fish-eating marine birds differs fundamentally from that in marine mammals.

Age Factors↗

Mirex in seals.

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Adipose Tissue↗

Effects of human diets on biotransformation enzyme activity and metabolic activation of carcinogens in rat liver.

We studied the effects of a complete human diet, based on mean consumption figures in The Netherlands, the heating of food, and the presence of vegetables and fruit in the diet on the drug metabolizing capacity of the rat liver and on metabolic activation of known carcinogens. Groups of five male and five female Wistar rats were given ad lib. one of six different diets for 3 months. Each diet contained 40 energy (E)% fat, 13 E% protein, 47 E% carbohydrate and 5% fibre (w/w). The diets were as follows: a control diet of semi-synthetic materials (A); a human diet of meat, bread and eggs without processing (B); diet B heated under usual household conditions (C); a diet representing a complete human meal including (summer) vegetables and fruit (D); diets consisting of winter vegetables (E) or summer vegetables (F) with fruit. Semi-synthetic components were added to diets B-F to achieve the desired composition. There were differences between male and female rats on the effects of the different diets on hepatic enzyme activity. In female rats, but not in males, ethoxyresorufin-O-deethylase activity was increased significantly (P less than 0.05) in groups C, D and E in comparison with the controls (group A). In male rats ethoxycoumarin-O-deethylase activity was enhanced in groups D, E and F, and glutathione-S-transferase was markedly induced in group F (P less than 0.01). In males, hepatic cytochrome P-450 was significantly (P less than 0.05) increased in groups B, C and E. There was no effect on aminopyrine-N-demethylase activity and almost no effect on UDP-glucuronyltransferase activity in either sex. Microsomes from rats fed heated food (C) markedly increased the mutagenicity of benzo[a]pyrene (B[a]P) in the Ames assay using Salmonella typhimurium strain TA98, in comparison with levels using microsomes from rats fed the raw food (B). Vegetables and fruit decreased B[a]P mutagenicity. All human diets except D decreased the mutagenicity of N-nitrosodimethylamine in tester strain TA100. The results indicate that the influence of components of human diets on rat-liver drug metabolism may have quite different effects on the biotransformation of carcinogens activated by different metabolic pathways.

Animals↗