ABSTRACT
The systemic effects of the radiation protective agent, S-3-(3-methylaminopropylamino) propylphosphorothioic acid (WR-151327), were studied in unirradiated B6CF1 male mice. Fifty mice were injected intraperitoneally with 540 mg/kg WR-151327, and groups of five mice were sacrificed at 14-day intervals up to and including 140 days post-treatment. Ten mice served as sham-injected controls. A necropsy was performed and gross morphological abnormalities were noted. Tissues (brain, eyes, harderian gland, salivary glands, sternal bone marrow, thyroid, lung, thymus, esophagus, trachea, skeletal muscle, heart, liver, kidney, adrenal gland, spleen, small intestine, pancreas, and testes) were fixed in 10% formalin, embedded in paraffin, and sectioned. Slides were routinely stained with hematoxylin and eosin while Alizarin red stain was used to test specifically for the presence of calcium salts. Histopathological effects of WR-151327 were restricted to the testes, salivary gland, and pancreas. The caudal pole of the testes was observed to undergo progressive changes from coagulation necrosis to dystrophic calcification. The cells of the submandibular salivary gland showed mainly hyperchromatic nuclei while the pancreas showed enlarged islets of Langerhans.
Subject(s)
Organothiophosphorus Compounds/toxicity , Radiation-Protective Agents/toxicity , Animals , Male , Mice , Pancreas/drug effects , Seminiferous Tubules/drug effects , Submandibular Gland/drug effectsABSTRACT
The specific activities of UDP-galactose : GM2 galactosyltransferase and CMP-NAN : GM1 sialyltransferase were measured in total particulate fractions of individual hepatocellular carcinomas (hepatomas) and hepatic nodules, induced in the rat by a carcinogenic diet of 0.05% N-2-fluorenylacetamide alternating with a low protein basal diet. In all tumors except the smallest nodules, galactosyltransferase specific activities were increased compared to those of control livers from rats fed only basal diet. When relative specific activities were related to wet weight of nodules larger than 0.1 g were in two populations. Specific activities of nodules in one population overlapped those of poorly differentiated hepatomas whereas specific activities of the second population those of well differentiated hepatomas. Specific activities of the sialyltransferase were also increased above those in control livers but not with the same frequency or to the same extent as for the galactosyltransferase. As with galactosyltransferase, nodules were found in two major populations when specific activities were related to nodule wet weight. The data suggest that increased specific activities of galactosyltransferase and sialyltransferase in hepatic nodules may provide an early phenotypic indicator of diverging differentiation in hepatocarcinogenesis.
