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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Since it has been shown that pregnancy protects the mammary gland from chemically induced carcinogenesis, this study was designed with the dual purpose of determining whether treatment of young virgin rats with the placental hormone chorionic gonadotropin (hCG) mimics pregnancy-induced changes in the tumourigenic response of the mammary gland and also whether the effect induced by both pregnancy and hormonal treatments was transitory, or a more permanent one, exerting the same effect when the period of time between delivery or termination of treatment and exposure to the carcinogen is lengthened. Virgin Sprague-Dawley rats were utilised in two experimental protocols. For protocol I, 50 day-old rats were either mated (Group II), or started receiving a daily intraperitoneal injection of 100 IU hCG (Group III) at age 50. Age-matched untreated virgin rats were used as controls (Group I). Twenty-one days after either delivery or termination of treatment all the animals received an intragastric dose of 8 mg DMBA/100 gbw. For the second protocol, 50 day-old virgin rats were also mated (Group V) or were treated with hCG for 21 days (Group VI); the resting period between delivery or termination of treatment was lengthened to 63 days, at which time they received a dose of DMBA. Age-matched controls (Group IV) received DMBA only. Tumourigenesis was evaluated 24 weeks post-carcinogen administration in all the groups. Pregnancy and hCG followed by the 21-day resting period significantly depressed mammary carcinogenesis to 11% and 6% respectively, compared with 63% in control animals. When the resting period was prolonged to 63 days there was also a significant depression in adenocarcinoma incidence to 9% in pregnancy (Group IV) in which it was observed that tumour incidence was also reduced as a consequence of aging at the time of exposure to the carcinogen. These results clearly indicate that hCG is as efficient as pregnancy and significantly reduces mammary carcinogenesis, and that the protective effect of both pregnancy and hCG treatment is long-lasting and both are more efficient than aging in reducing mammary carcinogenesis.
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PMID:Comparative study of the influence of pregnancy and hormonal treatment on mammary carcinogenesis. 191 Nov 88

The present study investigated the problem of whether or not the intake of an Western-style diet will induce within the host a specified hormonal change that increases the risk for breast cancer (BC). The key observations obtained are as follows: 1) The risk for BC in Japan has been increasing for the last 20 years in parallel with the Westernization of dietary habits (increase of fat and animal protein in the diet). 2) A Japanese BC patient is distinguishable from a corresponding normal control by (a) an increase of waist/hip ratio (more specifically, an increase of abdominal fat) and (b) a decrease in the number of live births (relative infertility). Height, weight and height-adjusted weight all cannot distinguish the former from the latter. 3) The former is also distinguishable from the latter by dual steroidal disorders of ovarian dysfunction (progesterone depression) and hypercorticoidism, as revealed by a case control comparison of urinary steroid excretions. 4) The long-term maintenance of an experimental mouse on a fat-rich diet increased abdominal fat weight at an adult age, but not at a young age. 5) In the same experiment, the fat-rich diet produced a reduction of plasma progesterone at an early stage, and also produced dual changes of progesterone depression and corticosterone stimulation at a late stage of experiment. Plasma estradiol was little affected by an excess of dietary fat. 6) In an adult mouse, the weight of abdominal fat was increased by corticosterone treatment and was decreased by estradiol treatment. The suppressive effect of estradiol on abdominal fat weight was dose-dependent. In conclusion, our findings seem to suggest the possibility that a fat rich diet may produce dual steroidal disorders of ovarian dysfunction and hypercorticoidism which in turn will open the way to breast carcinogenesis by activating 2 proto-oncogens at the initiation and promotion steps.
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PMID:Nutrition and breast cancer risk in Japan. 206 29

Eight-week-old male Sprague-Dawley rats were exposed to the carcinogen methylnitrosourea (MNU) via gastric intubation at doses of either 10 or 20 mg/kg body wt. Rats were treated once a week for 4 weeks, then once every 2 weeks for 1 month, for a total of 6 treatments. MNU was found to exert no consistent significant immunosuppressive effects in vivo as measured by spleen natural killer (NK) cell cytotoxicity, interleukin-2 (IL-2) production by splenic lymphocytes and prostaglandin E2 (PGE2) production by adherent peritoneal macrophages. In contrast, splenic NK cell cytotoxicity and IL-2 production of MNU-treated rats were actually elevated at several of the later sampling periods. PGE2 production was also elevated in MNU-treated rats in the later sampling periods. Body weights of MNU-treated rats were markedly decreased as early as 4 weeks following the initial MNU treatment. This suppression persisted throughout the study. The most dramatic change in organ weights was seen in the thymus. Thymus weights of all MNU-treated rats were significantly decreased 1 day after treatment and persisted for 4 weeks. By the 60 day sampling period, thymus weights were not significantly different from controls. However, by 120 and 180 days, thymus weights again were significantly lowered in those rats receiving MNU. These changes in thymus weights were accompanied histologically by initial cortical thinning and progressive loss of cortical thymocytes followed by the appearance of hyperplastic and neoplastic cells. It thus appears that the carcinogenic effect of MNU is not related to a depression of the immune surveillance system, at least as measured by NK cell activity.
Carcinogenesis 1990 May
PMID:The effects of methylnitrosourea (MNU) on natural killer (NK) cell cytotoxicity and cytokine production in rats. 218 3

The effects of carcinogenic nickel [(Ni) CAS: 7440-02-0] and Ni compounds on the natural killer (NK) cell activity of rat peripheral blood mononuclear cells (PBMCs) were studied. Rhabdomyosarcomas were locally induced by one im injection of Ni or Ni subsulfide [(Ni3S2) CAS: 12035-72-2] dust in the hind leg of WAG rats. A weakly tumorigenic dose of 5 mg Ni3S2 (tumor incidence, 2%) induced a transient decrease of PBMC NK activity against YAC-1 cells in vitro (from the 17th to the 23d wk after Ni3S2 inoculation), which could be restored by in vivo injections of partially purified rat fibroblastic interferon (IFN). Injection of 20 mg Ni (tumor incidence, 47.5%) produced a long-lasting depression of NK cell activity (from the 8th to the 23d wk). In vivo chronic IFN treatment of the Ni-injected rats neither restored NK cell activity nor affected the tumor incidence. However, NK cells of Ni-treated animals responded normally to IFN in vitro. Prospective analysis of individual NK cell responses showed that a persistent depression of basal NK cell activity was restricted to rats that subsequently developed a tumor. In these animals the time between carcinogen treatment and clinical detection of the primary tumor was positively correlated with the mean level of NK cell activity (3-4 determinations/rat). Admixture of manganese to Ni inhibited the development of tumors and also prevented the depression of NK cell activity produced by Ni alone. Noncarcinogenic Ni oxide stimulated NK cell activity. These results point out the possible involvement of NK cells in resistance to Ni-induced carcinogenesis.
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PMID:Inhibition of rat natural killer cell function by carcinogenic nickel compounds: preventive action of manganese. 243 44

The mitogenic effect of nafenopin and clofibrate in the liver is paralleled by a decreased utilization of [14C]thymidine for kidney DNA synthesis. Analogous changes in the liver and kidney DNA biosynthesis after nafenopin administration occur if [14C]orotic acid is added as a precursor of DNA pyrimidines. There is a time correlation between the uptake of labeled thymidine and its utilization for DNA synthesis in the liver during the initial stages of the mitogenic effect of the drug. Later on--after administration of a low dose of nafenopin or of repeated doses of clofibrate--the specific activity of DNA thymine does not differ from the values observed with the control group: the total radioactivity of the thymine components of the acid-soluble extract is even increased. The existence of a correlation between decreased utilization of [14C]thymidine for DNA synthesis and the total radioactivity of the thymine components of the acid-soluble extract in kidney can be observed only during the early stages after nafenopin administration. Subsequently, when the depression of the specific activity of kidney DNA thymine still persists, the specific activity of the thymine components of the acid-soluble extract does not differ from control values. The utilization of [14C]thymidine for DNA synthesis in the kidney is decreased after repeated clofibrate administration only 24 h after the last dose of the drug; these values later increase and even exceed control values. The total radioactivity of the thymine components of the kidney acid-soluble extract is unchanged.
Carcinogenesis 1988 Jan
PMID:Effect of nafenopin and clofibrate on uptake and utilization of labeled thymidine for DNA synthesis in rat liver and kidney. 244 97

Supplementation with increasing quantities of selenium (Se), as sodium selenite, to cultures of rat mammary epithelial cells resulted in a proportional depression in 7,12-dimethylbenz[a]anthracene (DMBA) binding to DNA. A depression in the two major anti bay-region dihydrodiol epoxide-deoxyribonucleoside adducts largely accounted for the reduced binding. DMBA-DNA binding in freshly isolated mammary cells from rats fed a diet containing 2.0 p.p.m. Se and incubated in culture with DMBA for 24 h was decreased 32% compared to binding in cells obtained from rats fed 0.1 p.p.m. Se. DMBA-DNA binding in mammary cells obtained from rats fed supplemental Se for 2 weeks or more was depressed compared to that occurring in cells from unsupplemented rats. The reduced ability of cells obtained from rats previously fed a 2.0 p.p.m. Se diet to activate DMBA to intermediates capable of binding to DNA became increasingly apparent with the duration of exposure to the carcinogen. Consistent with the in vitro supplementation study, cells isolated from rats previously fed a diet containing 2.0 p.p.m. Se had a reduced occurrence of the two major anti dihydrodiol epoxide adducts. The depression in DMBA binding following selenite supplementation, both in vitro and in vivo, supports the ability of Se to inhibit the initiation phase of carcinogenesis.
Carcinogenesis 1989 May
PMID:In vitro and in vivo effects of sodium selenite on 7,12-dimethylbenz[a]anthracene--DNA adduct formation in isolated rat mammary epithelial cells. 253 14

Keratinocytes from mouse skin were cultured for a short period in vitro following single or multiple treatments at low dose levels in vivo with the known chromosome-damaging agent triethylenemelamine (TEM). The chemical was applied to the skin of HRA/Skh hairless mice at concentrations corresponding to those reported to initiate cancer in initiation-promotion assays. A significant dose-related depression in keratinocyte cell recovery occurred over the dose range 0.3-1 mg TEM/mouse (single or multiple treatments). Under the same conditions, a dose-related induction of micronuclei was observed using the cytokinesis-block method with cytochalasin B. A similar frequency of micronuclei was detected in binucleate cells from mice treated with single or multiple applications of TEM. Mice held for 12-48 h post-treatment, before removal of skin for in vitro culture, yielded highest micronuclei frequencies. These results indicate that the same target cell population, skin keratinocytes, can be used to investigate both genotoxicity and carcinogenesis, and that micronucleus induction in these cells may be a sensitive signal of skin cancer initiation.
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PMID:Initiating carcinogen, triethylenemelamine, induces micronuclei in skin target cells. 275 23

The role of long-time immune suppression in carcinogenesis induced by the long-lived internal emitter 90Sr, is investigated in an ongoing study. The experimental design is based on the assumption that impaired immune responsiveness, by other means than 90Sr, might increase the neoplastic response in exposed individuals, and thus reflect a protective function, if existing. Intercomparison is made of the tumour yield in mice exposed to different single doses of 90Sr and simultaneously subjected or not to long-term immune suppression by adult thymectomy (ATx) and/or antilymphocyteglobulin (ALG) treatment. Information on the general condition and responsiveness of the immune system, in the respective models, during tumour expectancy time, is essential for a conclusive evaluation of the results. To meet these demands the present paper reports on histopathologic alterations in immune organs and changes in white blood cell counts, induced by the different combinations of 90Sr, ATx and ALG treatment. The results confirm the prediction, that ATx + ALG is an efficient and, with respect to the purpose of the study, suitable treatment for additive long-term depression of the immune system in 90Sr irradiated mice, evidenced in particular by increased depletion of monomorphonuclear cells (MNC) in lymphoid organs and peripheral blood. Subsequent reports will deal with functional immune parameters.
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PMID:Influence of 90Sr, adult thymectomy and antilymphocyteglobulin on haematopoietic tissues and peripheral blood leucocytes in CBA mice. 301 60

Groups of hairless (hr/hr) mice were given a single, topical skin application of either 50, 5 or 0.5 micrograms 7,12-dimethylbenz[a]anthracene (DMBA). At different times up to 3 days after treatment epidermal DNA distribution patterns were determined by flow cytometry, and sp. act. of DNA and labeling indices were obtained based on incorporation of [3H]thymidine. Mitotic rates were determined by the Colcemid method, and the number of basal and suprabasal cells were scored in histological sections. All three doses of DMBA led to an early depression in the uptake of [3H] thymidine, associated with an accumulation of cells with S phase DNA content peaking at 16 h. By combining the methods for studying DNA synthesis, it can be concluded that the alterations observed probably were due to a slow rate of DNA synthesis in the S phase cells, rather than to a block at the entrance of cells into the S phase. Three days after the application, DMBA still maintained an effect on the cell cycle progression, at least in the S phase. There was an obvious dose-response relationship in the inhibition of epidermal DNA synthesis. Six hours after application of the two highest doses of DMBA an early increase in the mitotic rate was observed. This short-lasting high mitotic rate was followed by a transient, very brief increase in the number of suprabasal cells. Thereafter a decrease in both the mitotic rate and the number of suprabasal cells occurred, probably caused by the alterations in DNA synthesis. After the lowest dose there was no such early increase in the mitotic rate and no initial, short-lasting increase in the number of suprabasal cells. Hence, this study shows that decreasing doses of DMBA provoke decreasing degrees of the same type of cell kinetic perturbations in the epidermal cell cycle.
Carcinogenesis 1987 Oct
PMID:Cell kinetic effects of low doses of the skin carcinogen 7,12-dimethylbenz[a]anthracene on hairless mouse epidermis. 311 12

The mechanisms of carcinogenesis are not known in detail, but there is strong evidence that cancer usually arises from a single transformed cell. Hence, although the process of carcinogenesis appears to require a multiplicity of changes in the affected cancer-forming cell, such as may be associated with successive stages of tumour initiation, tumour promotion, and tumour progression, only one such change induced by radiation in an appropriate cell may be conceived to increase the probability of neoplasia in a suitably susceptible individual. For this reason, carcinogenic effects of radiation, like mutagenic effects of radiation, are considered for purposes of radiological protection to have no threshold and to behave as stochastic phenomena. In contrast, certain other effects of radiation, such as cataract of the lens, infertility, and depression of the bone marrow, require the killing of many cells in the affected organs. Thus, they vary in severity with the extent of cell loss and have thresholds of detectability which depend on the sensitivity with which the consequences of cell loss can be measured.
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PMID:Cancer induction and non-stochastic effects. 354 59


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