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Biomedical subjects

J M Rice

Publications and source records attributed to J M Rice.

At least 163 records · Page 9Linked to original sources
PubMed1983

Dissimilar patterns of promotion by di(2-ethylhexyl)phthalate and phenobarbital of hepatocellular neoplasia initiated by diethylnitrosamine in B6C3F1 mice.

Potentially preneoplastic hepatocellular hyperplastic foci and hepatocellular neoplasms were studied in weanling male B6C3F1 mice that received a single i.p. injection (80 mg/kg) of diethylnitrosamine (DEN) at 4 weeks of age, followed by oral administration of phenobarbital (PB) or di(2-ethylhexyl)-phthalate (DEHP) that began 2 weeks after DEN injection and continued for up to 6 months. PB was administered in drinking water at 500 p.p.m. and DEHP in the feed at 3000, 6000 or 12 000 p.p.m. Groups of mice were sacrificed at 2, 4 and 6 months after DEN exposure; formalin-fixed liver samples were evaluated histologically. Hepatocellular neoplasms and foci of hyperplasia were quantified with the aid of an image analysis computer. Few foci were seen at 2, 4 or 6 months in mice exposed to DEN, PB or DEHP alone, while numerous foci and neoplasms were seen in mice given DEHP or PB after DEN. Area-perimeter measurements for each hepatocellular focus or neoplasm transection revealed that foci and neoplasms in PB-exposed mice increased both in size (area and volume) and in number throughout the study. In DEHP-exposed mice the pattern of response was different in that the numbers of foci did not increase between 4 and 6 months, but the foci increased in mean diameter and volume throughout the experiment. Foci and tumors appeared earlier in mice given higher dietary levels of DEHP than in those given lower doses. By the end of the study the number of foci per unit volume of liver was similar in mice given any dose of DEHP, but their volume was dose-related. Hepatocellular foci and neoplasms in PB-exposed mice were composed predominantly of eosinophilic hepatocytes, while in DEHP-exposed mice, basophilic foci and neoplasms predominated; the latter were more malignant in appearance than neoplasms in PB-exposed mice. At 6 months, the neoplasms in high dose DEHP-exposed mice were significantly larger than those in PB exposed mice. Histochemistry, however, revealed similarities between lesions in mice exposed to PB or DEHP. PB given continuously for 6 months revealed no initiating activity of DEHP given once by gavage and followed by PB in drinking water. Both morphology and biology of hepatocellular foci and neoplasms, which develop in mice after a single exposure to a carcinogen with initiating activity, thus depend, in part, on the subsequent promoting agent. More than one process of tumor promotion, as characterized by a specific sequence of morphologic and biochemical changes, is possible for the mouse hepatocyte.

Adenoma↗
PubMed1981

Histochemical characteristics of spontaneous and chemically induced hepatocellular neoplasms in mice and the development of neoplasms with gamma-glutamyl transpeptidase activity during phenobarbital exposure.

The histochemical characteristics of spontaneous hepatocellular neoplasms in mice of both sexes were examined and compared with those of hepatocellular neoplasms induced in female mice by administration of polycyclic aromatic hydrocarbon carcinogens as initiators with or without subsequent phenobarbitone treatment. Controls treated with phenobarbitone alone was also induced. Spontaneous neoplasms in the livers of mice rendered siderotic by subcutaneous iron injection were deficient in cellular accumulation of stainable iron. Glucose-6-phosphatase activity was deficient in the majority of spontaneous and induced neoplasms. ATPase activity was increase in about half of spontaneous and carcinogen-induced neoplasms but all induced neoplasms in mice treated with phenobarbitone showed deficient activity. Gamma-glutamyltransferase activity was present in very few of the spontaneous neoplasms or in the neoplasms induced in the absence of phenobarbitone administration. However, all induced neoplasms in the mice receiving phenobarbitone showed some degree of gamma-glutamyltransferase activity together with deficient glucose-6-phosphatase and ATPase activities. It is concluded that the histochemical characteristics of spontaneous or induced mouse hepatocellular neoplasms are variable and may be influenced by the inducing factors.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1981

Prenatal susceptibility to carcinogenesis by xenobiotic substances including vinyl chloride.

The carcinogenicity of vinyl chloride for experimental animals when administered transplacentally is reviewed in comparison with known transplacental carcinogens, including those that, like vinyl chloride, are dependent on enzyme-mediated metabolic conversion to a reactive intermediate in maternal or fetal tissues. Vinyl chloride is converted by mixed-function oxidases to the reactive metabolite chlorooxirane, the carcinogenicity of which is also reviewed. Vinyl chloride is unequivocally a transplacental carcinogen for the rat. No evidence exists, however, to support the hypothesis that exposure of male rats to vinyl chloride or any other carcinogen confers an increased risk of tumor development on their progeny. Many structural analogs of vinyl chloride, i.e., substituted ethylenes, are also carcinogenic for adult animals, and can with confidence likewise be predicted to be effective transplacental carcinogens.

Animals↗
PubMed1981

Pathology of gestational choriocarcinoma induced in patas monkeys by ethylnitrosourea given during pregnancy.

A rapidly fatal neoplastic disease with histological and clinical features resembling gestational choriocarcinoma in humans has been observed in patas monkeys. Timed pregnant females were given ethylnitrosourea (ENU) intravenously at doses of 0.1 to 0.4 mmol/kg body weight, beginning on day 30 of gestation and continuing weekly for a total of 12 injections. Of 59 monkeys given ENU during pregnancy, four of 12 subjected to the highest dose and three of the remaining 47 given lower doses died of choriocarcinoma within six months of cessation of ENU exposure. Death was usually caused by exsanguinating haemorrhage. At necropsy, tumour deposits were always numerous in the lungs and were frequently observed in abdominal viscera. An obvious primary uterine tumour was never found, and only one small primary was detected grossly. Sub-endometrial masses of tumour cells were generally observed microscopically, invading the endometrial stroma and forming endovascular tumour deposits in the veins. Both uterine and extrauterine tumour deposits were highly haemorrhagic, often partially necrotic, and consisted of cytotrophoblast-like cells with frequent mitoses, a high degree of cellular pleomorphism and variable but often prominent cytoplasmic glycogen. This tumour was never seen in males or non-gravid adult females. Chorionic gonadotrophin assays conventionally used for human and macaque samples were negative in both normally pregnant and tumour-bearing patas, and did not contribute to the diagnosis. Trophoblast of patas monkeys appears highly susceptible to the carcinogenic effects of ENU and provides an animal model for gestational choriocarcinoma.

Animals↗
PubMed1981

Reversible inhibition of rat hepatocyte proliferation by hydrocortisone and its effect on cell cycle-dependent hepatocarcinogenesis by N-methyl-N-nitrosourea.

The susceptibility of hepatocytes to carcinogenesis in vivo may be influenced by the phase of the cell cycle at which carcinogen-induced damage is incurred. In order to better understand this relationship, hepatic cell proliferation in juvenile male Fischer 344 rats was charted following a two-thirds partial hepatectomy. For hepatocytes, two distinct waves of DNA synthesis occurred which were followed after 6 to 8 hr by waves of mitotic cell division. In contrast to this kinetic pattern, when hydrocortisone was given after the partial hepatectomy, the initial waves of DNA synthesis and mitosis by hepatocytes were each delayed by about 15 hr. In rats not given hydrocortisone, susceptibility to heptocarcinogenesis by N-methyl-N-nitrosourea was greatest at 20 hr after partial hepatectomy when the peak fraction of proliferating hepatocytes was in the S phase. By shifting the time of onset of DNA synthesis, the hydrocortisone treatments also shifted the time with greatest sensitivity to N-methyl-N-nitrosourea, with hepatocytes in late G1 or S again the most susceptible. Numerous tumors were also induced by N-methyl-N-nitrosourea in extrahepatic tissues, including intestine, Zymbal's gland, nervous system, kidneys, odontogenic tissues, and peritesticular mesothelium. The results illustrate the importance of cell proliferation in carcinogenesis and further point to the specific sensitivity of certain cell cycle phases.

Animals↗
PubMed1981

Regional blood flow, capillary permeability, and glucose utilization in two brain tumor models: preliminary observations and pharmacokinetic implications.

Regional quantitative autoradiographic measurements of blood flow, capillary permeability, and glucose utilization were made in rats harboring an intracerebral Walker 256 metastatic tumor or a well-differentiated oligodendroglioma. Distinct differences were observed between the two brain tumor models; regional differences within the metastatic tumor appeared to be partly related to tumor size. The pharmacokinetic implications of these physiological measurements with respect to drug delivery to tumor tissue are discussed. The interrelationship of commonly used parameters to quantitate transport across the blood-brain barrier--permeability coefficient, permeability-surface area product, transfer constant, extraction fraction, equilibrium half-time, and blood flow--and their relevance to effective brain tumor chemotherapy are demonstrated.

Animals↗
PubMed1981

Pathogenesis of toxic and neoplastic renal lesions induced by the flame retardant tris (2,3-dibromopropyl)phosphate in F344 rats, and development of colonic adenomas after prolonged oral administration.

Male F344 rats, 4 weeks old, were given tris (2,3-dibromopropyl)phosphate (TBP) via stomach tube at a dosage level of 100 mg. per kg. of body weight per day. Treatment was given 5 days per week and continued for 4 or 52 weeks. Representative treated and control animals were killed at predetermined time intervals and the histomorphology and ultrastructure of the kidneys investigated. Twenty-four hours after the first TBP treatment, the epithelial cells at the corticomedullary junction developed increased nucleus to cytoplasm ratios, cytomegaly, and nuclear vacuolization and pleomorphism. These changes increased in severity to a toxic tubular nephrosis as treatment continued, and extended to the peripheral cortex by 52 weeks. Electron microscopy showed loss of microvilli and polarity in the epithelium of the proximal convoluted tubules. The development of adenocarcinomas from hyperplastic areas at these sites were studied. At the ultrastructural level, the cytoplasm of the neoplastic cells was poorly differentiated, and in many areas, the surfaces of the cells were covered by microvilli. In one group of rats, treatment was terminated after 4 weeks. In these animals, a gradual but incomplete restoration of the tubular epithelia to nearly normal morphology was observed. Nuclear changes persisted after cytoplasmic abnormalities had disappeared. At 52 weeks, three of five surviving rats given TBP throughout the experiment were found to have polypoid adenomas of the descending colon.

Adenoma↗
PubMed1980

Alteration by phenobarbital of membrane-associated enzymes including gamma glutamyl transpeptidase in mouse liver neoplasms.

Administration of phenobarbital for 5 to 7.5 weeks to aged C3HfB/HeN mice with spontaneous liver tumors produced an enhancement of gamma glutamyl transpeptidase activity in the tumors and a decrease in glucose-6-phosphatase and adenosine triphosphatase activity. Discontinuation of phenobarbital feeding for 5.5 weeks resulted in the loss of gamma glutamyl transpeptidase activity in tumors. These findings of alterations in three membrane-associated enzymes indicate that phenobarbital produces substantial changes in the composition of cellular membranes which may be related to its promoting activity.

Adenosine Triphosphatases↗
PubMed1980

Endocardial schwannomas in rats. Their characterization by light and electron microscopy.

Thirty male Sprague-Dawley rats were given a single intravenous injection of methyl(acetoxymethyl)nitrosamine. Primary endocardial tumors developed in ten rats. By light and electron microscopy, the tumors had many of the typical features of schwannomas (neurinomas) in rats. Tumors were composed of masses of elongated cells surrounded by a fine reticulin network, occasionally forming Verocay bodies. Basement membrane was observed on the external surfaces of tumor cells, which had convoluted plasma membranes. To our knowledge, this is the first report of a spontaneous endocardial schwannoma in a rat. The literature addressing endocardial tumors in rodents and man is discussed, and criteria for distinguishing this neoplastic entity from other tumors and non-neoplastic endocardial proliferations are described.

Animals↗
PubMed1979

Effects of thymosin on cytotoxicity and virus production in AKR mice.

The cytotoxic potential and ability to produce endogenous ecotropic virus(es) of thymic-, splenic-, and lymph node-derived lymphocytes were significantly (and differentially) altered following thymosin treatment of young (nonleukemic) and aged (preleukemic) AKR mice. Thymosin administration markedly enhanced the cytotoxic potential of both splenic and lymph node lymphocytes from aged animals, but effected a moderate increase only in the spleens of young mice. Thymosin enhanced the production of endogenous virus(es) by thymocytes from aged mice, with the opposite effect noted in young animals. Splenectomy generally reduced the cytotoxic activity and virus titers of lymphocytes from both groups, and thymosin administration further reduced the cytotoxic response. These findings probably reflect overall effects on both regulatory lymphocyte subpopulations and different endogenous viruses in young and aged mice.

Aging↗
PubMed1979

Mesotheliomas and proliferative lesions of the testicular mesothelium produced in Fischer, Sprague-Dawley and Buffalo rats by methyl(acetoxymethyl)nitrosamine (DMN-OAc).

A single intraperitoneal dose of methyl(acetoxymethyl)nitrosamine (13 mg/kg body weight) given to 78 5-week-old male rats induced 25 mesotheliomas; two mesotheliomas were found in 67 control rats. All mesotheliomas arose from the peritesticular mesothelium and had a typical microscopic appearance of branching papillary fronds with a collagenous core covered by one or many layers of plump tumor cells. Cytoplasm of tumor cells contained material that reacted positively to a colloidal iron stain and was labile to hyaluronidase. In addition to frank mesotheliomas, 16 lesions, which we called atypical mesothelial proliferations, were found. These consisted of a single focus of plump mesothelial cells overlying an area of thick stroma. Often these foci included short, non-branched papillary projections above the surface of adjacent normal mesothelium. Twelve of the 16 lesions occurred in methyl(acetoxymethyl)nitrosamine-treated rats.

Animals↗