Diet-induced obesity modulates epigenetic responses to ionizing radiation in mice.

Both exposure to ionizing radiation and obesity have been associated with various pathologies including cancer. There is a crucial need in better understanding the interactions between ionizing radiation effects (especially at low doses) and other risk factors, such as obesity. In order to evaluate radiation responses in obese animals, C3H and C57BL/6J mice fed a control normal fat or a high fat (HF) diet were exposed to fractionated doses of X-rays (0.

Nature of nontargeted radiation effects observed during fractionated irradiation-induced thymic lymphomagenesis in mice.

Changes in the thymic microenvironment lead to radiation-induced thymic lymphomagenesis, but the phenomena are not fully understood. Here we show that radiation-induced chromosomal instability and bystander effects occur in thymocytes and are involved in lymphomagenesis in C57BL/6 mice that have been irradiated four times with 1.8-Gy γ-rays.

Rag-dependent and Rag-independent mechanisms of Notch1 rearrangement in thymic lymphomas of Atm(-/-) and scid mice.

The pathways of thymic lymphomagenesis are classified as Rag-dependent or -independent according to their dependence on recombination-activating gene (Rag1/2) proteins. The role of the two-lymphoma pathways in oncogene rearrangements and the connection between lymphoma pathways and rearrangement mechanisms, however, remain obscure. We compared the incidence and latency of thymic lymphomas, and associated rearrangements of the representative oncogene Notch1 among Rag2(-/-), ataxia telangiectasia mutated (Atm)(-/-), and severe combined immune deficiency (scid) mice combined with Rag2 deficiency.

Existence of a threshold-like dose for gamma-ray induction of thymic lymphomas and no susceptibility to radiation-induced solid tumors in SCID mice.

Severe combined immune deficiency (SCID) mice exhibit limited repair of DNA double-strand breaks and are sensitive to ionizing radiation due to a mutation of the DNA-dependent protein kinase catalytic subunit gene. To elucidate the effects of deficient DNA double-strand break repair on radiation-induced carcinogenesis, the dose-response relationship for the induction of all tumor types was examined in wild-type and SCID mice. In wild-type mice, the incidence of thymic lymphomas at gamma-ray doses up to 1 Gy was almost equal to the background level, increased gradually above 1 Gy, and reached a maximum of 12.

Involvement of illegitimate V(D)J recombination or microhomology-mediated nonhomologous end-joining in the formation of intragenic deletions of the Notch1 gene in mouse thymic lymphomas.

Deregulated V(D)J recombination-mediated chromosomal rearrangements are implicated in the etiology of B- and T-cell lymphomagenesis. We describe three pathways for the formation of 5'-deletions of the Notch1 gene in thymic lymphomas of wild-type or V(D)J recombination-defective severe combined immune deficiency (scid) mice. A pair of recombination signal sequence-like sequences composed of heptamer- and nonamer-like motifs separated by 12- or 23-bp spacers (12- and 23-recombination signal sequence) were present in the vicinity of the deletion breakpoints in wild-type thymic lymphomas, accompanied by palindromic or nontemplated nucleotides at the junctions.

Radiation-induced deletions in the 5' end region of Notch1 lead to the formation of truncated proteins and are involved in the development of mouse thymic lymphomas.

Notch1 protein is a transmembrane receptor that directs various cell fate decisions. Active forms of Notch1 consisting of a transmembrane domain and an intracellular domain (Notch1TM) or only an intracellular domain (Notch1IC) function as oncoproteins. To elucidate the effect of Notch1 abnormalities in radiation-induced lymphomagenesis, we determined the structure of the Notch1 gene and examined the frequency and the sites of Notch1 rearrangements in radiation-induced mouse thymic lymphomas.

Absence of linkage between radiosensitivity and the predisposing atp7b gene mutation for heritable hepatitis in the LEC rat.

The LEC rat is known to be a mutant strain that spontaneously develops heritable hepatitis due to copper accumulation, caused by mutation of the copper-transporting ATPase gene (Atp7b). Immunodeficiency and radiosensitivity have also been observed. Hayashi et al.

Chemoprevention by dietary dehydroepiandrosterone against promotion/progression phase of radiation-induced mammary tumorigenesis in rats.

When pregnant rats received whole body irradiations with 260 cGy gamma-ray at day 20 of pregnancy, and were then implanted with a diethylstilbestrol (DES) pellet for an experimental period of 1 year under feeding of a control diet, a high incidence (96.2%) of mammary tumors was observed. Administration of dietary 0.

Relationship between stages of mammary development and sensitivity to gamma-ray irradiation in mammary tumorigenesis in rats.

Mature Wistar-MS rats were ovariectomized and treated with estradiol benzoate and/or progesterone. Control animals were treated with olive oil. The rats were then exposed to gamma-rays and implanted with a pellet of diethylstilbestrol.

Susceptibility of lactating rat mammary glands to gamma-ray-irradiation-induced tumorigenesis.

Lactating rats of the Wistar-MS strain were irradiated with 260 cGy of gamma rays 21 days after parturition (day 21). Diethylstilbestrol (DES) pellets were implanted one month after termination of nursing and were allowed to remain for one year. A significantly higher incidence (96.

Promotive effects of diethylstilbestrol, its metabolite (Z,Z-dienestrol) and a stereoisomer of the metabolite (E,E-dienestrol) in tumorigenesis of rat mammary glands pregnancy-dependently initiated with radiation.

Wistar-MS rats received whole body irradiation with 260 cGy gamma-rays at day 20 of pregnancy and then were treated with diethylstilbestrol (DES), E,E-dienestrol (E,E-DIES) or Z,Z-dienestrol (Z,Z-DIES) for 1 year. DES administration caused the highest incidence of mammary tumors with a concomitant reduction of gain in body weight. When E,E-DIES or Z,Z-DIES in pellet form was implanted, the incidence of tumors was significantly lower than that observed in rats treated with DES.

Influence of the estrous cycle at gamma-ray exposure on radiation-induced mammary tumorigenesis in virgin rats.

Wistar rats received whole body irradiation with 260 cGy gamma-rays at 10 a.m. of individual phases of their estrous cycle and then had diethylstilbestrol pellets implanted for 1 year.

Pregnancy-dependent initiation in tumorigenesis of Wistar rat mammary glands by 60Co-irradiation.

Pregnant Wistar rats received whole body irradiation with 260 cGy gamma-rays at days 7, 14 and 20 of pregnancy and then were treated with diethylstilbestrol (DES) for 1 year. The highest incidence (92.9%) for tumorigenesis of mammary glands was observed in the rats irradiated in late pregnancy.

Subcellular distribution of 3 beta-hydroxysteroid dehydrogenase-isomerase in bovine and murine adrenocortical tissue: species differences in the localization of activity and immunoreactivity.

Key to the production of biologically active steroids is the enzyme 3 beta-hydroxysteroid dehydrogenase-isomerase. Some controversy has arisen concerning the subcellular distribution of this enzyme within steroidogenic cells. The distribution of 3 beta-hydroxysteroid dehydrogenase-isomerase was assessed in subcellular fractions obtained from homogenates of rat, bovine, and mouse adrenal glands in two ways.

Reasons for reduced activities of 17 alpha-hydroxylase and C17-C20 lyase in spite of increased contents of cytochrome P-450 in mature rat testis fetally irradiated with 60Co.

Pregnant rats received whole body irradiation with 2.6 Gy gamma-ray from a 60Co source at Day 20 of gestation. When pups were 4 months old, activities of electron transport system and steroid monooxygenase in tests were assayed.

Steroidogenesis in the testes and the adrenals of adult male rats after gamma-irradiation in utero at late pregnancy.

Pregnant rats were irradiated with 2.1 Gy gamma-ray of 60Co at day 20 of gestation. Seventy days after birth, the body weight of the fetally irradiated male pups was significantly lower than the control.

Steroid hormone production in testis, ovary, and adrenal gland of immature rats irradiated in utero with 60Co.

Pregnant rats received whole-body irradiation at 20 days of gestation with 2.6 Gy lambda rays from a 60Co source. Endocrinological effects before maturation were studied using testes and adrenal glands obtained from male offspring and ovaries from female offspring irradiated in utero.

Leydig cell tumor of the ovary associated with endometrial carcinoma and containing 17 beta-hydroxysteroid dehydrogenase.

A case of ovarian Leydig cell tumor associated with adenocarcinoma of the endometrium in a 66-year-old woman is described herein, the eighth such case published. Clinically, both masculinizing and feminizing symptoms were observed: an increase in facial hair growth, slight baldness, clitoromegaly, and postmenopausal genital bleeding. Three biopsies of the endometrium during a 5-month preoperative period showed atypical hyperplasia.

Light and electron microscopic immunocytochemistry on the localization of 3 beta-hydroxysteroid dehydrogenase/isomerase in the bovine adrenal cortical cells.

The localization of 3 beta-hydroxysteroid dehydrogenase/isomerase (3 beta-HSD) was studied in bovine adrenal glands by light as well as electron microscopic immunocytochemistry, using anti-bovine adrenal 3 beta-HSD antibody. With light microscopy the cytoplasm of the glomerulosa cells was weakly immunostained, while that of the fasciculata-reticularis cells was intensely immunostained though both the capsular connective tissue cells and the medullary cells were entirely negative for this reaction. Electron microscopic immunocytochemistry revealed that the positive reaction products for 3 beta-HSD were present on the membrane of smooth endoplasmic reticulum of the cortical cells, especially that of the fasciculata and reticularis cells.

Immunocytochemical localization of 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD), and its relation to the ultrastructure of steroidogenic cells in immature and mature rat ovaries.

Immunocytochemical localization of 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) and its relation to the ultrastructure of steroidogenic cells were examined in mature and immature rat ovaries. In mature (8-10 weeks old) rat ovaries, the theca interna cells of secondary as well as Graafian follicles, and the interstitial gland cells were all strongly stained with anti-17 beta-HSD antibody. However, granulosa cells, corpus luteum cells, oocytes and peritoneal epithelial cells were negative against this staining.

Testicular and adrenal 3 beta-hydroxy-5-ene-steroid dehydrogenase and 5-ene-4-ene isomerase.

The purified multifunctional enzyme, 3 beta-hydroxysteroid dehydrogenase with steroid 5-ene-4-ene isomerase from rat testes and adrenals showed similar catalytic properties. They exhibited the same molecular weight of 46,500. Either NAD+ or NADH was required for steroid isomerizing activity, probably as an allosteric effector.

Purification and properties of testicular 3 beta-hydroxy-5-ene-steroid dehydrogenase and 5-ene-4-ene isomerase.

Through the treatment of rat testicular microsomes with sodium cholate, 3 beta-hydroxy-5-ene-steroid dehydrogenase and 5-ene-4-ene isomerase (abbreviated as the 3 beta-hydroxysteroid dehydrogenase and isomerase, respectively) were solubilized, and then purified by DEAE and hydroxylapatite column chromatographies. The findings were as follows: With this purification procedure, the 3 beta-hydroxysteroid dehydrogenase activity could not be separated from the isomerase. For 3-oxo-4-ene-steroid formation from 3 beta-hydroxy-5-ene-steroids, NAD+ was required as a cofactor.

Purification and characterization of rat adrenal 3 beta-hydroxysteroid dehydrogenase with steroid 5-ene-4-ene-isomerase.

After solubilization of rat adrenal microsomes with sodium cholate, 3 beta-hydroxysteroid dehydrogenase with steroid 5-ene-4-ene isomerase (abbreviated as steroid isomerase) activity was purified to a homogeneous state. The following characteristics of the enzyme were obtained: 3 beta-Hydroxysteroid dehydrogenase together with steroid isomerase was detected as a single protein band in SDS-polyacrylamide gel electrophoresis, where its mol. wt was estimated as 46,500.

Localization of epoxide-metabolizing enzymes in rat testis.

Antibodies raised against rat hepatic epoxide hydrolase (EC 3.3.2.