Journal of toxicology and environmental health. Supplement最新文献_第2页

Diethylstilbestrol metabolism in food-producing animals. 食源性动物对己烯雌酚的代谢。

Journal of toxicology and environmental health. Supplement Pub Date : 1976-01-01

P W Aschbacher

引用次数: 0

Estrogen-induced Leydig cell tumor in the mouse: a model system for the study of carcinogenesis and hormone dependency. 雌激素诱导的小鼠间质细胞肿瘤:一个研究癌变和激素依赖性的模型系统。

Journal of toxicology and environmental health. Supplement Pub Date : 1976-01-01

R A Huseby

{"title":"Estrogen-induced Leydig cell tumor in the mouse: a model system for the study of carcinogenesis and hormone dependency.","authors":"R A Huseby","doi":"","DOIUrl":"","url":null,"abstract":"Malignant neoplasms of endocrine tissues represent almost half of the cancers diagnosed clinically in the United States, and many of these respond to hormonal therapies. Estrogen-induced testicular Leydig cell tumors in the mouse would seem to represent a realistic model for the laboratory investigation of this significant group of cancers. Data accumulated over the past few years clearly show that the Leydig cell is a target tissue for estrogens. Administering large doses of estrogen results in a reduction of enzymes converting progesterone to testosterone and induces a transient, but quantitatively very significant, synthesis of DNA in the Leydig cells of tumor-susceptible strains of mice. Neither of these actions of estrogen is mediated via the hypophysis. It has been demonstrated that the Leydig cells have specific protein receptors in their cytoplasm that bind estrogens and transport them to the nucleus where they are also bound. The genetic composition of the Leydig cells themselves is extremely important for the development of tumors. An adequately functioning pituitary gland is also essential for tumor formation. Confining the testes to the abdomen results in enzyme changes similar to those produced by estrogen administration and significantly augments the development of Leydig cell tumors. Once tumors form they frequently are dependent for their continued growth on estrogenic stimulation and/or on a functioning hypothysis. Regressed tumors may remain dormant for many months only to resume progressive growth when placed in and adequate hormone environment.","PeriodicalId":76061,"journal":{"name":"Journal of toxicology and environmental health. Supplement","volume":"1 ","pages":"177-92"},"PeriodicalIF":0.0,"publicationDate":"1976-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"11234586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Testing the antifertility drug enovid for carcinogenesis in five strains of mice. 抗生育药物enovid在5个品系小鼠体内的致癌作用试验。

Journal of toxicology and environmental health. Supplement Pub Date : 1976-01-01

W E Heston

{"title":"Testing the antifertility drug enovid for carcinogenesis in five strains of mice.","authors":"W E Heston","doi":"","DOIUrl":"","url":null,"abstract":"In testing for any carcinogenic effect of certain hormones the choice of test strain or strains is extremely important. By selecting several inbred strains one obtains maximum genetic variability offering a greater chance of demonstrating carcinogenesis in regard to a number of organs or tissues. The five strains of mice chosen in this study (C3H/He, C3HfB/He, BALB/cHe, A/He, and C5BL/He) provided a test for effect of Enovid at sterilizing doses on occurrence of mammary tumors, ovarian tumors, hepatomas, cervical and vaginal tumors, adrenocortical adenomas, and hypophyseal tumors. Results indicated a slight inhibitor effect of Enovid on mammary tumors in C3H and adrenocortical adenomas in BALB/c and an even greater inhibiotry effect on hepatomas in C3HfB. No effect on ovarian tumors could be detected in the appropriate test provided by C3HfB. In BALB/c females epithelial lesions of the cervix and vagina were observed in both the treated females and the controls with a slight increase in the group treated with the highest dose. All were small lesions observed only in the histologic section. None had invaded beyond the wall of the vagina, and none had metastasized. None could be classified as a frank carcinoma. In the group treated with the highest dose of Enovid, the lesions showed slightly further progression than in the other groups. The most significant tumorigenic effect of the Enovid was the increase in hypophyseal tumors in the C5BL females at advanced age. Direct extrapolation from one strain to another, from one species to another, from mouse to humans, or from one human being to another would be risky because of genetic differences. Approaches to the problem in human beings are, however, suggested. Because of these observations in mice, it would be well, if possible, to collect hypophyses of women at postmortem who have previously been on birth control pills for some time and send these hypophyses to some central laboratory where they can be examined for any changes that might be attributed to the use of the antifertility drug.","PeriodicalId":76061,"journal":{"name":"Journal of toxicology and environmental health. Supplement","volume":"1 ","pages":"257-66"},"PeriodicalIF":0.0,"publicationDate":"1976-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12174391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Summary of the changes in the human female genital tract as a consequence of maternal diethylstilbestrol therapy. 摘要母体己烯雌酚治疗后人类女性生殖道的变化。

Journal of toxicology and environmental health. Supplement Pub Date : 1976-01-01

A L Herbst

引用次数: 0

Metabolic activation of carcinogenic diethylstilbestrol in rodents and humans. 致癌性己烯雌酚在啮齿动物和人类中的代谢激活。

Journal of toxicology and environmental health. Supplement Pub Date : 1976-01-01

M Metzler

引用次数: 0

Dose-dependent kinetics of diethylstilbestrol in the rat. 己烯雌酚在大鼠体内的剂量依赖性动力学。

Journal of toxicology and environmental health. Supplement Pub Date : 1976-01-01

H Neumann

引用次数: 0

Use of the neonatal mouse in studying long-term effects of early exposure to hormones and other agents. 用新生小鼠研究早期暴露于激素和其他物质的长期影响。

Journal of toxicology and environmental health. Supplement Pub Date : 1976-01-01

H A Bern, L A Jones, K T Mills

{"title":"Use of the neonatal mouse in studying long-term effects of early exposure to hormones and other agents.","authors":"H A Bern, L A Jones, K T Mills","doi":"","DOIUrl":"","url":null,"abstract":"The neonatal female mouse is considered as a model for studying the long-term consequences of exposure of the human fetus and neonate to hormones and other agents. Parallelism is noted between the results of administration of sex steroids and diethylstilbestrol (DES) to newborn mice and the phenomenon of vaginal cancer in young women whose mothers were given DES for threatened abortion. The progression of the neonatally steroid-treated mouse lesions from persistent vaginal cornification through hyperplastic lesions to tumors is described. The interaction of progesterone with estradiol is considered (lesions are fewer but more severe at 12 months of age following neonatal exposure to a combination of estradiol and progesterone), and the ability of neonatal progesterone treatment alone to result in cervicovaginal lesions in intact mice is emphasized. All steroids result in increased mammary tumor incidence and lowered age of tumor onset in intact mice bearing the mammary tumor virus; both the ovary and the virus are required for these effects. Possible ramifications of early perinatal exposure are indicated in regard to the male, to nongenital structures, to the endocrine system generally, and to immunologic mechanisms.","PeriodicalId":76061,"journal":{"name":"Journal of toxicology and environmental health. Supplement","volume":"1 ","pages":"103-16"},"PeriodicalIF":0.0,"publicationDate":"1976-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12175629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Chemical probes of estrogen action: affinity labeling. 雌激素作用的化学探针:亲和标记。

Journal of toxicology and environmental health. Supplement Pub Date : 1976-01-01

J A Katzenellenbogen, K E Carlson, H J Johnson, H N Myers

{"title":"Chemical probes of estrogen action: affinity labeling.","authors":"J A Katzenellenbogen, K E Carlson, H J Johnson, H N Myers","doi":"","DOIUrl":"","url":null,"abstract":"A systemic approach has been taken in the preparation and evaluation of photoaffinity labeling agents for the estrogen receptor from rat and lamb uterus. Several derivatives of estradiol and the nonsteroidal estrogen, hexestrol, containing photoreactive diazocarbonyl or azide functions have been synthesized. The receptor binding affinity of these compounds and their capacity to photointeract with the estrogen binding site (inactivate) can be assayed inderectly by competition assays. Several of the compounds that showed both resonably high binding affinities and inactivation efficiencies have been prepared in high specific activity, tritium-labeled form. Direct binding measurements with these derivatives in unpurified rat uterine receptor preparations, show that while these compounds bind to the receptor, they also show considerable nonspecific binding to nonreceptor proteins. Irradiation of these derivatives in rat uterine cytosol preparations results in incorporation of large amounts of radioactivity into protein in a covalent fashion. The amount of nonspecific labeling is so large, however, that estrogen site specificity (indicated by protection with unlabeled estradiol) cannot be demonstrated. More recently, we have used a partially purified receptor preparation from lamb uterus. The receptor in this preparation has been disaggregated by mild trypsinization and can be electrophoresed in native form. Electrophoretic analysis of the proteins in photolabeled preparations show some covalent incorporation into the receptor region of the gel with one derivative but not with another. The effectiveness of the photoaffinity labeling reagents prepared thus far is assessed, and suggestions are made for the design of new, more effective reagents.","PeriodicalId":76061,"journal":{"name":"Journal of toxicology and environmental health. Supplement","volume":"1 ","pages":"205-30"},"PeriodicalIF":0.0,"publicationDate":"1976-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12214299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Reflections on Second Annual NCTR Hormone Research Symposium. 第二届NCTR激素研究年会的思考。

Journal of toxicology and environmental health. Supplement Pub Date : 1976-01-01

R G Zimbelman

{"title":"Reflections on Second Annual NCTR Hormone Research Symposium.","authors":"R G Zimbelman","doi":"","DOIUrl":"","url":null,"abstract":"Hormones have widely different effects depending on species, dosage use, timing of dosage, route of administration, status of animals (re: pregnancy, stage of estrous cycle, age), and end point being measured. Hormones are essential to both maintenance and quality of life, and they occur in our environment with regularity. Hormones are seen by some persons as a regulatory dilemma because, when characterized under conditions of marked overdosage, the biological consequences are often undesirable. Because many of the naturally occurring hormones were identified long ago and have been studied for many decades, the reality is that much more knowledge is available on hormones than on more recently discovered substances, either naturally occurring or synthetic. The effects of hormones on tumors, either increases or decreases in incidence, appear to be indirect through alterations of normal physiological processes. The mechanism of action of hormones at the cellular level suggests that hormones are not involved in cancer by causing DNA changes, but in the degree of expression of changes in DNA that have occurred by other means. Key studies, especially at the molecular level, to further define the involvement of hormones in carcinogenesis should help us to define tolerance levels and aid with the regulatory dilemma.","PeriodicalId":76061,"journal":{"name":"Journal of toxicology and environmental health. Supplement","volume":"1 ","pages":"97-102"},"PeriodicalIF":0.0,"publicationDate":"1976-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"11234588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Study of prenatal DES exposure and its consequences in Rochester, Minnesota. 明尼苏达州罗彻斯特产前DES暴露及其后果的研究。

Journal of toxicology and environmental health. Supplement Pub Date : 1976-01-01

K L Noller, L T Kurland

引用次数: 0