By the use of acetylsalicylic acid (aspirin) 14C-labelled in either the acetyl or the carboxyl group, the metabolic pathway and the degree of degradation of the substance were studied. The change in aspirin concentration and the rate of degradation occurring in major tissues and organs after oral administration was measured by radioactivity techniques. The degree of degradation for the period 10-30 minutes was found to be about 38% in the stomach wall, 64% in the liver and 86% in the lung, and less than 10% in the circulating portion of aspirin itself in blood, under conditions of equilibrium concentration of substrate. A technique measuring 14CO2 in expired air and using 14C-acetyl aspirin allowed for determination of the kinetics of the transformation of this compound into salicylic acid. The effective period for aspirin for unstrained and unanesthetized rats given orally was determined to be 90 min. The metabolic fates of the two kinds of 14C-labelled aspirin given orally were found to be very different and characteristic by counting and autoradiographic techniques. The distribution of [carboxyl-14C] aspirin was rather uniform, but [acetyl-14C] aspirin preferentially accumulated in the bone cortex portion.

Administration, Oral↗

PubMedDate not supplied

Radiorespirometric patterns of [14C]-substrates in rats. II. Differences with the nature and administration route of the injection fluid.

The effects on the 14CO2 expiratory patterns of the nature and administration route of the injection fluid containing [14C]-glucose were studied. In the case of rapid intravenous injection, no difference in the radiorespirometric pattern was found with different glucose concentrations and volumes of the aqueous injection fluid. With intravenous injection, lower P1 heights and longer plateaus were recorded with the [14C]-glucose blood mixture as compared to the aqueous injection fluid. This result indicates that [14C]-glucose in the aqueous fluid injected into the blood vessel could be supplied into organs or tissues before mixing with the blood fluid in the blood vessel system. It is also suggested that larger amounts of [14C]-glucose are taken up into organs and tissues when the label was in aqueous solution rather than blood. In the case of intraduodenal infusion, a trace of glucose in a small volume (0.05 ml) of aqueous solution gave a similar radiorespirometric pattern to that given by intravenous injection of aqueous fluid. This indicates that there was fast absorption of glucose by the intestinal mucosa, which was not rate-limiting. A relatively large volume and very high concentration of glucose in the infusion fluid caused suppression of the radiorespirometric pattern. This may reflect physical suppression of intestinal peristalsis.

Animals↗

PubMedDate not supplied

The kinetics and dynamics of three kinds of radioactive methionine after i.v. administration in mice.

In C57BL mice, a tracer amount of methionine (Met) at a concentration approximate to that in the blood was administered in the tail vein (i.v.). The rates of endogenous metabolic decomposition of methionine were obtained by using three specifically labelled compounds, [1-14C]-Met, [m-14C]-Met and [35S]-Met. Results on the kinetics and dynamics after i.v. administration suggested that 5 min after administration, most of the labelled compounds were taken up into the organs and tissues, and only a small portion was excreted in the expired air as CO2, the final metabolite of methionine. At 30 min the radioactive concentration in blood was minimal and was consistent with the maximum of the 14CO2 excretion in expired air. Gradual increase of the radioactive concentration in blood after 30 min might be due to the contribution of the metabolite in the blood. Methionine taken up was endogenously utilized by more than 40% during 48 h and it maintained the order of [1-14C]:[m-14C]:[35S]. Out of the remaining 60%, 40% was metabolized in 6 h after administration, the [1-14C] moiety being excreted mainly into expired air, the [m-14C] moiety into expired air and urine, and the [35S] moiety mainly into urine and partly into faeces. Microautoradiograms revealed that a part of the last 20% was taken up into the enzyme proteins contained in the pancreatic juice and intestinal juice, and was decomposed within 48 h.

Animals↗

PubMedDate not supplied

Autoradiographic characterization of newly developed melanoic cell group different from the melanoic tumor piece embedded into a liver lobe of mice.

Secondary proliferous melanoic tumors grew at 100% of probability in a liver lobe of C57BL/6 mouse with a piece of B16 melanoma tumor embedded successfully in the lobe. Clear border between host liver tissues and the embedded tumor piece was observed 14 days after embedding. No division image was noted in cells of the embedded tumor piece. In all regions surrounding the embedded tumor piece, there were few accumulations of leucocytes, lymphocytes, or giant cells, indicating a strong likelihood of immune reaction or antigen-antibody reaction, although there was active formation of fibroblast bunds and production of lysosomal enzymes. Secondary proliferous melanoic tumors developed in the environment of liver tissue separately from the embedded tumor location. Results of 14C-thymidine-nuclear labeling of embedded tumor cells showed that the majority of the labeled cells did not migrate or divide. In the case of 14C-thymidine-labeling of host liver tissue cells, results indicated no transfer of 14C-radioactivity into nuclei of embedded tumor cells, although there was positive distribution of 14C-radioactivity into nuclei of proliferous cells in the secondary tumor, a newly developed melanoic cell group. When prelabeling was performed the average density of autoradiographic image over the secondary tumor was equivalent to that over the normal liver tissue at the early stage such as 7 days after embedding and decreased with time after that. The newly developed melanoic cells were particularly exciting and proliferous, because they received much more labeling of 14C-thymidine as compared to liver tissue cells that was provided by one shot labeling of the radioactive tracer 1 h. before sacrifice of tumor embedded mice. There was no development of secondary melanoic cells in the liver lobe in case of embedding of a tumor piece previously by wrapping with a membranefilter, less 5 microns in pore size.

Animals↗