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Biomedical subjects

J M Rice

Publications and source records attributed to J M Rice.

At least 181 records · Page 10Linked to original sources

Perinatal period and pregnancy: intervals of high risk for chemical carcinogens.

Experiments in rodents indicate that during the post-embryonic period of prenatal development, the fetus is more sensitive than the adult to certain carcinogens, by several decimal orders of magnitude. Most such agents are direct-acting and independent of metabolism. To other substances, often those which require enzyme-mediated metabolic conversion to a chemically reactive derivative in order to effect carcinogenesis, the fetus may be less vulnerable than the adult. The neonate is also more susceptible than adults to some carcinogens, and may be more susceptible than the fetus to certain agents. Both rodent and primate studies indicate that gravid females are also at elevated risk for carcinogenesis, in part because of the presence in the placenta of trophoblastic tissue which may become malignant. The contributions of rapid growth rate, changing metabolic competence, and tissue differentiation to elevated perinatal susceptibility to carcinogens in rodents and primates are discussed, together with the implications of these findings for human beings subjected to industrial or environmental exposures to such chemicals.

Adult↗

Spontaneous preeclamptic toxemia of pregnancy in the patas monkey (Erythrocebus patas).

A disease characterized by edema, proteinuria, hypoproteinemia and hypertension was seen in late gestation in patas monkeys. The initial sign was edema of the perineum, ankles and lower trunk. The onset was abrupt, occurring 7 days or less prepartum. The affected animals were not depressed, and convulsions were not seen. In 6 of the 98 pregnancies during a 1-year period, symptoms of the disease were present. The highest incidence was manifested by primiparous animals with 3 of 36 pregnancies affected. Two of 38 second pregnancies and 1 of 24 third pregnancies were also affected. Five of the animals recovered spontaneously and were normal 14 days postpartum. Edema persisted for 30 days in one female. This animal continued to be hypertensive and had persistent mild proteinuria and hypoproteinemia. She was killed approximately 1 year postpartum due to severe renal disease. The spontaneous disease seen in patas monkeys resembled toxemia of pregnancy in humans more closely than the experimentally induced disease in other animals.

Animals↗

Transplacental effects of ethylnitrosourea in a nonhuman primate, Erythrocebus patas.

A breeding colony of the Old World monkey Erythrocebus patas, an African species, has been established to study transplacental carcinogensis in a representative primate species. ENU was administered by repeated iv injections to pregnant females and to juveniles of both sexes. Repeated doses of 0.1 mmole/kg body weight per injection, given at 14-day intervals, are tolerated without apparent signs of toxicity by fetal and by pregnant and nonpregnant adult or juvenile monkeys. The internal can be reduced to 7 days, at least during the latter two-thirds of pregnancy. Large single doses (1.0 mmole/kg) are tolerated by pregnant females but are frequently abortifacient. These doses produce acute cytolytic damage to the cells of the periventricular germinal matrix in the fetal brain. Studies with [14C]ethyl-ENU indicate that there is no placental barrier to this carcinogen. As of December 1975, no tumors had been observed.

Animals↗

Problems and perspectives in perinatal carcinogenesis: a summary of the conference.

The proceedings of the Conference are summarized in the context of current understanding of perinatal susceptibility to carcinogenic agents. The consequences of exposure to either metabolism-dependent or direct-acting chemical carcinogens during fetal or neonatal life are quantitatively different from the effects of comparable doses of the same agents in adults. The nature of these differences and their relevance both for preventive medicine and for application to bioassay procedures for detection of suspected carcinogens are discussed for conventional (chemically reactive) carcinogenic compounds and for hormones. The degree of tissue differentiation at the time of exposure to a carcinogen and the genetics of the subject have been shown to affect susceptibility to induction of embryonal and differentiated types of tumors and by both chemical agents (including hormones) and viruses. The desirability of conducting parallel studies in two or more species when investigating mechanisms of perinatal/adult differences in susceptibility to carcinogens is emphasized.

Animals↗

Transplacental and neonatal induction of neurogenic tumors in mice: comparison with related species and with human pediatric neoplasms.

The literature on chemical induction and natural occurrence of neurogenic tumors in mice and some unpublished data from our laboratories are reviewed. Neurogenic tumors are a minor component of the total tumorigenic response of mice to alkylating agents such as ENU and MNU. In comparison with rats, a given dose of ENU induces a much lower incidence of neurogenic tumors in mice, and the mean latency is much longer than in rats. Although most neurogenic tumors induced by ENU in mice by either transplacental or direct postnatal exposure are of glial or Schwann cell origin, as in rats, and occur most frequently in the cerebrum or cranial nerves, respectively, medulloblastomas of the cerebellum also occur in treated mice. Transplacental and neonatal exposure to ENU were much more effective in inducing neurogenic tumors than treatment later in life. Ependymomas were not seen in mice, although they are common in ENU-treated rats. Neuroblastoma of the adrenal medulla, a common human pediatric tumor, has not been induced to either species, but it does occur spontaneously in mice. The induction by ENU of medulloblastomas demonstrates that this rodent equivalent of an embryonal tumor of the human nervous system can result from exposure to exogenous chemical agents.

Animals↗

A survey of growth in soft agar and cell surface properties as markers for transformation in adult rat liver epithelial-like cell cultures.

Continuous epithelial-like cell lines derived from normal adult rat liver and hepatocarcinomas were evaluated for their growth in soft agar and five properties of the cell membrane as markers for neoplastic transformation. A correlation of these properties was made to the tumorigenicity of the lines in nude mice. Growth in soft agar was a specific and sensitive marker, whereas the data on uptake of 2-deoxy-D-glucose were consistent, with high uptake being a specific but clearly not a sensitive marker. Agglutination and hemadsorption mediated by concanavalin A, multinucleation in the presence of cytochalasin B, and the cell membrane activity of adenosine triphosphatase did not correlate with tumorigenicity of the other markers for transformation. In addition, it is shown that Mycoplasma infection does not alter any of these properties but that infection can be eliminated by passage of cells through nude mice.

Animals↗

The resistance of spontaneous mouse hepatocellular neoplasms to iron accumulation during rapid iron loading by parenteral administration and their transplantability.

Spontaneous mouse liver nodules were found to be resistant to iron accumulation induced either by dietary overload or by a rapid protocol of subcutaneous injection of iron dextran. Transplants of 11 liver nodules into the mammary fat pad gave rise to neoplastic growth. Transplants of the less differentiated nodules grew more frequently and rapidly than better differentiated nodules and produced pulmonary metastases. Therefore, these mouse liver nodules are considered to be neoplasms, and their resistance to iron accumulation suggests that this marker will be useful in studying their histogenesis.

Animals↗

Histocompatibility difference between C3HfeB/HeN and C3H/HeN mice: tumour induced in C3HfeB/HeN mice expresses C3H/HeN-associated alloantigen.

A transplacentally induced lung tumour of C3HfeB/HeN mouse origin expresses, as a tumour-associated antigen, a normal tissue component of strain A mice. The genetic locus coding for this alloantigen has been shown to be linked to the H-2 major histocompatibility complex. In the present study we demonstrate that this antigen is also expressed on normal tissues of C3H/HeN mice. Skin grafts exchanged between C3HfeB/HeN and C3H/HeN mice are reciprocally rejected at approximately 3 weeks after grafting. C3HfeB/HeN mice were derived from C3H/HeN mice in 1945. These strains have apparently deviated since then in their genetic regulation of the expression of the MHC-linked genetic locus. The finding of the C3H/HeN-associated antigen on a C3HfeB/HeN mouse-derived lung tumour indicates that this deviation is reversible.

Animals↗

Growth and hematologic development of the patas monkey (Erythrocebus patas) to one year of age.

Data from 338 blood samples of 31 patas monkeys is presented to show the normal hematolgoic development from birth to one year of age, and is compared to 120 samples from normal adults. Marked changes in hematocrit, hemoglobin, red cell numbers, and leukocyte distribution which occurred during the first month were followed by a slow progression to adult values. Body weight data is also presented which shows a linear growth rate during the first year of life.

Age Factors↗

Granular cell variants in a rat schwannoma. Evidence of neurogenic origin of granular cell tumor (myoblastoma).

A large, intraabdominal rat schwannoma had numerous granule-containing cells cytologically identical to cells of granular cell tumor (myoblastoma). The small eosinophilic granules stained positively by the periodic acid-Schiff (PAS) reaction, with intensity not reduced by diastase pretreatment. Granules stained positively with the Tibor Pap silver impregnation for reticulin and by electron microscopy were identical to myoblastoma cell granules. The nuclei of granular cells were morphologically identical to those of the neoplastic Schwann cells. The granular cells were in numerous foci within the tumor, frequently were seen in mitosis, and possessed an extremely variable volume of cytoplasm. They seemed to evolve from neoplastic Schwann cells. Cells with only a narrow perinuclear rim of granular cytoplasm were of the same size and general configuration as adjacent neoplastic Schwann cells, while cells with increasing volumes of granular cytoplasm were increasingly swollen and round. One area of the tumor was composed almost entirely of such large cells and was histologically identical to classic granular cell tumor.

Animals↗

Establishment of a persistent measles virus infection in HEp-2 cells.

A productive measles virus persistent infection has been established in HEp-2 cells. Greater than 90% of the persistently infected HEp-2 cells (H2MV) exhibited measles specific immunofluorescence and haemadsorption. Although most of the H2MV cells contained measles specific antigens, only a small percentage (less than 1%) actually produced infectious measles virus as determined by infectious centre assays. The measles virus produced by H2MV cells exhibited properties different from the initiating parent Edmonston strain virus, being reduced in virulence and also temperature sensitive for replication at 39 degrees C. The role of these altered virus properties in the establishment of persistence is considered.

Antigens, Viral↗

Selective induction of intestinal tumors in rats by methyl(acetoxymethyl)nitrosamine, an ester of the presumed reactive metabolite of dimethylnitrosamine.

Methyl(acetoxymethyl)nitrosamine (DMN-OAc) was synthesized and tested for toxicity and carcinogenicity in rats to test the hypothesis that alpha-hydroxylation is required for metabolic activation of dimethylnitrosamine (DMN) to a reactive, proximate carcinogen. The acute median lethal doses (LD50) of DMN-OAc and DMN injected ip into 5-week-old male Sprague-Dawley (Charles River (CD) rats were determined to be 0.19 and 0.59 mmole/kg body weight or 25 mg DMN-OAc/kg and 44 mg DMN/kg body weight, respectively. Single ip injections of one-half the LD50 DMN-OAc (13 mg/kg body weight) in 5-week-old rats of both sexes resulted in a high incidence of epithelial tumors of the intestinal tract. Mean survival times for rats with intestinal tumors were 353 days for males and 433 days for females. Tumors were rarely found at other sites. DMN at equivalent toxic (one-half the LD50, 22 mg/kg) and molar (= one-sixth LD50, 7.0 mg/kg) dose levels, yielded (as expected) tumors of kidneys, lungs, and occasionally other organs, but at a much lower incidence. The finding of the potent carcinogenicity of DMN-OAc supported the postulate that alpha-hydroxylation of DMN in vivo generates a proximate carcinogen.

Adenocarcinoma↗