Whole-body autoradiographic study on the distribution of 3H-cryptolepine in mice.

The distribution of 3H-cryptolepine in pigmented and albino mice and in pregnant mice on day 16 of gestation was studied by whole-body autoradiography, after a single intravenous injection. The labelled compound rapidly left the blood and was localized in most tissues, except for the central nervous system where no radioactivity could be observed. The most pronounced decrease of concentration occurred between 1 and 4 hours postinjection.

Differential distribution and placental transport of 2- and 3-t-[methyl-14C]butyl-4-hydroxyanisole (BHA) in pregnant mice.

The placental transport and localization in fetal and maternal tissues of 14C-BHA isomers, 2-t-[methyl-14C]butyl-4-hydroxyanisole (2-BHA) and 3-t-[methyl-14C]butyl-4-hydroxyanisole (3-BHA), were studied in pregnant mice by whole-body autoradiography techniques. BHA isomers were given (iv 50 microCi/100 g as a tracer dose) to pregnant mice at Day 11 (organogenesis) and Day 18 (postorganogenesis) of gestation. Peak levels of radioactivity occurred in various tissues 1-4 hr after iv administration of both isomers.

Computer-assisted quantification and image processing of whole-body autoradiograms.

A computerized image-processing system especially adapted for analysis of whole-body autoradiograms has been developed. It consists of commercially available standard components, including a black-and-white video camera, a microcomputer, and graphics equipment. The lower performance of the hardware has been compensated for by more flexible software.

Selective incorporation of thiouracil into murine metastatic melanomas.

The uptake and retention of 14C-thiouracil and 125I-thiouracil in small lung metastases of B16 murine melanoma was studied in beige mice injected intravenously with melanoma cells. By impulse counting of excised tumor and organ pieces, a high concentration of radioactivity was found in the lung metastases, as compared to normal tissues. The highest tumor/organ concentration ratios appeared 24 h after injection of the radiolabeled thiouracil.

Rate of incorporation of [3H]thymidine in various tissues of the mouse. A basis for the evaluation of genotoxic effects of chemicals.

[3H]Thymidine has been extensively used as a selective precursor to DNA in studies on the kinetics of cell proliferation. We have become interested in measuring early inhibition of the DNA synthesis in various organs of intact animals for detecting genotoxic properties of chemicals. Such experiments should, for convenience and to achieve a large capacity, be performed in the simplest way possible.

Tissue-specific inhibition of [3H]thymidine incorporation into DNA by carcinogenic N-nitrosamines.

The N-nitrosamines N-nitrosodimethylamine (DMN), N'-nitrosonornicotine (NNN) and 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) were injected intraperitoneally 24 h before sacrifice in F344 rats and C57BL mice in doses of 297 mumoles/kg b.w. and 148 mumoles/kg b.

Whole-body autoradiography using 11C with double-tracer applications.

This paper reports that it is possible to obtain good autoradiographic pictures of a 11C-labelled compound ([11C]methionine) in spite of the short half-life of 20 min by modifying the whole-body autoradiographic (WBA) technique. Double radionuclide autoradiography was performed by utilizing the great difference between the half-lives of 11C and 14C or 35S. The first exposure resulted entirely from 11C, and the second exposure the day after from 14C or 35S, respectively.

The in vivo uptake of tritiated thymidine as a potential short-term test of toxic effects of polycyclic aromatic hydrocarbons in different organs.

A rapid in vivo test for toxicity is described where the test substance is allowed to distribute and metabolize in the intact mouse. Quantitative data are provided on the effect of 3 different polycyclic aromatic hydrocarbons on the DNA turnover in various organs, measured as the incorporation of tritiated thymidine. In accordance with previously reported carcinogenic potencies, 7,12-dimethylbenz[alpha]anthracene (DMBA) was more potent in inhibiting the thymidine incorporation than benzo[alpha]pyrene (B[alpha]P).

Selective affinity of dimethyl sulphoxide (DMSO) and 2-amino-4-phenylsulphonylbenzenesulphonamide (NSD 3004) for the large intestinal mucosa of mice.

Whole-body autoradiography of 14C-labelled dimethyl sulphoxide and 35S-labelled 2-amino-4-phenylsulphonylbenzenesulphonamide revealed a selective accumulation of labelled substance in the large intestinal mucosa of mice. The mechanism of accumulation is discussed with regard to previous results on sulphone-containing compounds with tissue-specific distribution patterns.

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 whole body autoradiographic study on the distribution of 14C-labelled di-(2-ethylhexyl)phthalate in mice.

Di-(2-ethylhexyl)phthalate (DEHP), a plasticizer used for polyvinylchloride polymers, has been reported to leach from blood transfusion bags and the plastic material in hemodialysis units into the blood. Phthalate esters are known to be hepatotoxic and teratogenic in experimental animals. Reports on the distribution and metabolism of DEHP indicate that the compound in largely excreted from the body within a few days.

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.

Whole-Body Autoradiography.

Ever since its introduction in the early 1950s whole-body autoradiography has been used quite extensively for mapping the fate of various substances in the body, especially in the fields of pharmacology and toxicology. A detailed description of the whole-body autoradiographic technique is given. Some factors of general interest are dealt with-such as radionuclides and labeled substances, followed by a number of illustrations providing details and specific references.

Long-term fate of [14C]nicotine in the mouse: retention in the bronchi, melanin-containing tissues and urinary bladder wall.

N-methyl-14C and 2'-14C-labelled nicotine were used for whole-body autoradiographic distribution studies on C57BL- and NMRI-mice. Radioactivity was retained in the melanin-containing tissues, in the bronchial walls, and in the urinary bladder wall, up to 1 month after administration. The activity levels in the bronchi decreased faster if [2'(14)C] nicotine was used.

Distribution of an 125I-labelled chloroquine analogue in a pregnant macaca monkey.

Whole body autoradiography of a pregnant monkey (Macaca irus) of late gestation was performed 72 h after an intravenous injection of the 125I-labelled chloroquine analogue 4-(3-dimethylaminopropylamino)-7-iodoquinoline (DAPQ). The overall distribution pattern in the monkey was similar to that which was earlier observed in rodents. A few species differences, however, were found in the monkey as compared to the rodents: a high accumulation in the inner part of the adrenal cortex, a high level in the central nervous system, and generally a higher retention in the tissues.

Distribution of local anesthetics: accumulation in some endocrine polypeptide-hormone producing cell systems.

1 After the injection of labelled procaine and lidocaine in mice, the location and concentration of radioactivity was demonstrated by autoradiographical methods.2 An accumulation in some endocrine cells such as the pancreatic islets, the hypophysis, the adrenal medulla and certain cells of the thyroid (probably representing the calcitonin-producing parafollicular cells) was shown.3 After the injection of [(14)C]-procaine in chicks, an accumulation of radioactivity was observed in the ultimobranchial gland (which produces calcitonin in birds), but not in the thyroid.