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L Dencker

Publications and source records attributed to L Dencker.

At least 91 records · Page 5Linked to original sources
PubMed1983

Thioamides as false melanin precursors: studies in murine melanomas.

Melanotic melanomas show a high rate of melanin synthesis. Foreign substances that are accepted as precursors in the formation of melanin may therefore be useful in the diagnosis and therapy of malignant melanotic melanomas, if labelled with suitable radionuclides. We have earlier reported that 2-thiouracil is incorporated in melanotic melanomas, apparently as a false melanin precursor. In the present study it is shown that methimazole and 5-iodo-2-thiouracil are as well accepted as melanin precursors. 5-Iodo-2-thiouracil is of special interest, since iodine has many clinically useful radioisotopes. The chemical properties that characterize substances which are incorporated as false precursors into melanin are discussed. A free sulfur ligand of the thioamides (2-thiouracil, 5-iodo-2-thiouracil, methimazole and thiourea are all incorporated into melanin) seems to be essential and the link between these substances and the melanin. Uracil (which lacks sulfur) and 2-benzylthiouracil (where the sulfur is blocked with a benzyl group) do not attach to melanin. Our conclusion therefore is that the thioureylene structure is the smallest common molecular fragment of the false melanin precursors.

Amides↗
PubMed1982

TCDD embryotoxicity in the mouse may be enhanced by beta-naphthoflavone, another ligand of the Ah-receptor.

The significance of the aryl hydrocarbon (Ah)-receptor (which binds 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and a number of polycyclic hydrocarbons) in murine embryonic tissues for the teratogenic action of TCDD has been studied. The receptor has been localized, especially to the embryonic maxillary region. When the non-teratogenic beta-naphthoflavone (beta-N), which is another ligand of the Ah-receptor, was co-administered with TCDD it increased the frequency of cleft palate compared with the number induced by TCDD alone. This was true when beta-N was administered simultaneously or 8 h before TCDD but not 24 h before or after. Fetal death was induced even when the two compounds were administered at wider intervals. It is suggested that TCDD and beta-N partly induce a battery of enzyme systems leading to the final malformation.

Animals↗
PubMed1982

A new melanoma seeker for possible clinical use: selective accumulation of radiolabelled thiouracil.

In a previous report we have shown that a few substances, especially thiouracil, are incorporated as false precursors into melanin during its synthesis. In the present investigation, we have intensified our studies on the incorporation of thiouracil into melanotic melanomas. Firstly, the distribution and retention of both 14C- and 35S-labelled thiouracil in mice with transplanted melanomas were studied. A high and selective accumulation was found in the melanotic tumours. The concentration in the rest of the body was low, with the exception of the thyroid gland. Secondly, melanoma-bearing mice were given increasing doses of thiouracil, and cultured melanoma cells were exposed to different concentrations of thiouracil, to investigate the relation between dose and uptake in melanomas and melanoma cells, respectively. A relatively linear increase in uptake with dose was found, indicating that the melanin incorporation of thiouracil is non-saturable up to subtoxic levels.

Animals↗
PubMed1982

Accumulation of 125I-labelled thiouracil and propylthiouracil in murine melanotic melanomas.

We have shown that thioamides are incorporated as false precursors into melanin during its synthesis. To be clinically useful in the diagnosis or therapy of melanotic melanomas, they would have to be tagged with an appropriate isotope or possibly a cytotoxic moiety. 125I-Thiouracil (125I-TU) is here shown to be accumulated in the melanin of melanotic melanomas transplanted into mice in a similar way as is 14C-thiouracil (14C-TU). 125I-TU gives tumour/liver and tumour/muscle ratios up to 22 and 778 respectively, at 4 days after administration. 125I-TU is accumulated by melanoma cells in vitro more effectively than 14C-TU (125I-TU/14C-TU, 2.7), while the in vivo accumulation into melanomas is slightly lower for 125I-TU as compared to 14C-TU (125I-TU/14C-TU, 0.35). This appears to be due to a partial deiodination (less than 14% of the dose within 4 days) and probably a more rapid excretion of 125I-TU or its metabolite(s). The accumulation of radioactivity in the thyroid can essentially be eliminated by pretreatment with potassium iodide and/or thyroxine. 125I-Propylthiouracil is also accumulated in melanotic melanoma cells in vivo and in vitro, but at a lower level than in 125I-TU and 14C-TU.

Animals↗
PubMed1982

Autoradiographic studies on the distribution of arsenic in mice and hamsters administered 74As-arsenite or -arsenate.

Whole-body autoradiography in combination with other determinations of tissue levels of 74As-arsenic in mice, 5 min. to 30 days after intravenous injections of 74As-arsenite (As III) or -arsenate (As V), showed higher organ concentrations and whole-body retention of arsenic in the As III mice as compared to the As V mice. Only the kidneys (at short time intervals) and the skeleton had higher levels in the As V mice as compared to the As III mice. The skeletal accumulation of As V is probably due to the resemblance of the arsenate to phosphate, so that arsenate may substitute for phosphate in the apatite crystal. The long-term retention of arsenic was most apparent in hair and skin, squamous epithelium of the upper gastrointestinal tract (oral cavity, oesophagus, and the oesophageal part of the stomach mucosa), the epididymis, thyroid, lens and skeleton. The accumulation in hair, skin and the upper gastrointestinal tract may be ascribed to a binding to keratin, the content of which is high in squamous epithelia. The distribution of arsenic in golden hamsters was similar to that found in mice. The significance of the findings in relation to reported adverse effects of inorganic arsenic is discussed.

Animals↗
PubMed1982

Disposition of chemicals in the developing embryo and fetus.

The uptake of foreign compounds and their distribution in the embryo and fetus at different stages of gestation are reviewed. In particular studies performed by means of autoradiography are discussed. It is shown that a number of compounds may be almost completely blocked by the placental structures early in gestation, although they are foreign compounds. In late gestation often one or a few organs may accumulate a particular compound; this may be due to metabolism, affinity for tissue components, etc. In some cases the site of accumulation of tissue binding of a drug has correlated well with the teratogenic or carcinogenic effects.

Adrenal Glands↗
PubMed1982

Fetal uptake and distribution of metallic mercury vapor in the mouse: influence of ethanol and aminotriazole.

The placental transport of mercury in pregnant mice and its localization in the embryo and fetus from early organogenesis through the whole fetal period was studied by whole-body autoradiography and gamma counting. Metallic mercury (203Hg0) (after inhalation) was compared to inorganic 203HgCl2 (after i.v. injection). Hg0 appears to be oxidized to Hg2+ in the fetal tissues and Hg0 inhalation results in about 4-fold higher fetal mercury concentration than Hg2+ injection (9.9 versus 2.4% gram dose per gram tissue). Preadmission to the dams with ethanol or aminotriazole resulted in higher fetal concentrations (especially in the liver) of mercury after inhalation of Hg0 but not after injection of Hg2+. A high placental concentration and accumulation in the corpora lutea of mercury after Hg0 inhalation should be also noted.

Amitrole↗
PubMed1981

Incorporation of thiouracil and some related compounds into growing melanin.

Several drugs, mainly polycyclic amines, are accumulated in melanin-containing tissues. They are bound to preformed melanin (both in vivo and in vitro). Thiouracil is accumulated into melanin according to another principle: It is incorporated as a false precursor during melanin formation. It is thus taken up only in growing melanin, e.g. in the eye of pigmented mouse foetuses or in melanomas. The acceptance of a foreign substance during the formation of a foetal tissue seems theoretically important. We are also interested in the practical viewpoint of using false melanin precursors as selective melanoma seekers. Some related substances are therefore compared with respect to incorporation into growing melanin. The thiouracil uptake in the ocular melanin of a 5 day old mouse was 276 times higher than that of a 3 month old mouse based on weight units of melanin. Thiourea is incorporated in growing melanin as well but also binds slightly to preformed melanin. Uracil and fluorouracil showed no specific uptake into growing melanin. It thus seems as if the sulfur is essential for the incorporation into the melanin polymer. 35S-thiouracil and 2-thio(2-14C)urcal showed the same high uptake, indicating that at least part of the uracil moiety is incorporated together with the sulfur. There seems to be a relation between the property to be incorporated into melanin and the tyrostatic activity. Both in the formation of melanin and thyroid hormones, tyrosine is the physiological precursor and both reactions are catalyzed by oxidizing enzymes. Properly labelled thiouracil derivatives seem to be promising melanoma seekers for diagnostic and radiotherapeutic purposes.

Animals↗
PubMed1981

Autoradiographic localization of 35-S-furosemide at different stages of its renal excretion.

The renal localization of 35-S-activity was studied by autoradiography at different times (1/2 min intervals) following the rapid injection of a bolus of 70 micrograms 35-S-furosemide into the renal portal system of hens. After removal, both kidneys were freeze-sectioned, freeze-dried and subjected either to apposition autoradiography according to Ullberg or to microautoradiography. There was extensive labelling over cortical areas of the ipsilateral kidney, in the periphery of lobuli, the site of proximal tubular cells. This labelling was maximal at 1 and insignificant already at 4 min post injection. At this time, however, there was a distinct patchy labelling corresponding to collecting ducts. At 7 min post-injection no specific labelling was found. The findings suggest that furosemide in the peritubular blood is accumulated in proximal tubules, rapidly transferred (tubular secretion) to their lumina and carried distally by the tubular fluid, subsequently resulting in high concentrations of the diuretic in the lumina of collecting ducts. Thus the findings are in keeping with the view that active tubular secretion of furosemide in the hen contributes significantly to a high luminal concentration of the drug in more distal parts of the tubules, the likely site of diuretic action.

Animals↗
PubMed1981

Distribution of 35S in mice after oral administration of alpha-dithioacetamidinium chloride. An autoradiographic investigation.

The distribution of 35S in mice has been investigated by whole-body autoradiography after oral administration of the 35S labelled S-75 (2,2'-Dithiobis(N-[(1-adamantyl)-methyl]-acetamidine)dihydrochloride). The substance was rapidly absorbed, and the highest concentration occurred in the liver and kidneys. During the highest radiation protective activity (after about 45 min) a substantial concentration was found in the red pulp of the spleen. This supports previous findings that S-75 has its most marked protective effect on the splenic haemopoiesis. Previously, it was shown that cysteamine is more evenly distributed in the body than S-75, which is in agreement with its more generalized protective effect than S-75.

Acetamides↗
PubMed1979

An autoradiographic study on the fate of 65Zn in zinc-rich tissues in some rodents.

Whole-body autoradiography of 65Zn, administered as 65ZnCl2, in mice showed a high initial radioactivity in several parenchymatous organs. Some other tissues showed a rather slow accumulation and a pronounced retention of 65Zn. This applied to the pancreatic islets, which showed the highest soft-tissue radioactivity at most survival intervals and in which 65Zn was detected still 60 days after a single dose. 65Zn was also retained in the hippocampus of the brain, the dorsolateral prostate, Paneth cells in the intestine, the bone and the hair. A few guinea-pigs and rabbits were studied. In the guinea-pigs, there was no specific labelling of the pancreatic islets. The rabbits showed the highest soft-tissue radioactivity in the mandibular salivary gland. Most tissues which retained a high level of 65 Zn have previously been reported as containing high levels of endogenous zinc. The results of the present study indicate that there is a slow zinc-turnover in these tissues.

Animals↗
PubMed1977

Trypan blue accumulation in the embryonic gut of rats and mice during the teratogenic phase.

Four to 48 hours after iv and sc administration of teratogenic doses of trypan blue to rats and mice the uterus was removed and rapidly frozen, after having been placed in a horizontal plane, and frozen sections were attached to tape and dried at a low temperature. By this procedure embryos and placental structures were present in the same sections and loss or redistribution of the dye was minimized. The dye was found in the yolk-sac cavity and to be accumulated in the visceral (proximal) endoderm. It was also acculmulated in the embryonic endoderm--forming the embryonic gut. This accumulation occurred after the administration of the trypan blue up to the time of closure of the vitelline duct, which occurs at 11 days postconception in rats and 9.5 days in mice. None was found when injection was made after this closure. No dye was detected in the ecto- and mesodermal layers. The period of embryonic uptake of trypan blue largely corresponds with the period of teratogenic sensitivity in these species as reported by others.

Animals↗
PubMed1976

Preparation of cross-linked human serum albumin labelled with 125I for studies of reticuloendothelial system function.

A method is described to prepare a new test substance for reticuloendothelial system (RES) function studies. Glutaraldehyde was used for the cross-linking of human serum albumin. The polymeric product was fractionated by repeated chromatography on Sepharose 6B. Cross-linked material with a particle size of approximately 18 nm, as evidenced by electron microscopy, was pooled and labelled with 125I. The surface charge of the albumin polymers, determined by agarose gel electrophoresis, was not significantly changed compared with that of the original albumin monomer. Cross-linking takes place almost entirely between the epsilon-amino groups of lysine in the albumin molecules, as confirmed by amino acid analysis. Preliminary biological tests on mice indicate that the cross-linked polymers are phagocytosed mainly by RE cells of the liver and spleen. The disappearance rate was similar to that of other RE test substances. Intravenous administration of more than 50 times the usual dose caused no deaths, indicating a very low toxicity. Trace amounts of glutaraldehyde were not detectable by gas chromatography. Judging from these experiments, this new preparation of cross-linked albumin fulfils many of the criteria stated for an ideal RES test substance.

Animals↗
PubMed1976

Uptake and retention of 133Ba and 140Ba-140La in mouse tissues.

The distribution of barium in the mouse has been determined qualitatively by whole-body autoradiography after i.v. administration of 133BaCl2 solution. The quantitative distribution of 104Ba and 140La has been analyzed after i.p. injections of the two nuclides in equilibrium by measuring the activity in excised organs in a two-channel scintillation counter. Approximate doses to the eyes and different parts of the skeleton have been calculated.

Animals↗