UMLS:C0011570 - FACTA Search

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

Trout were fed a range of dietary components which altered their carcinogenic response to aflatoxin B1 (AFB1). Dietary protein at levels substantially exceeding nutritional requirements were synergistic with AFB1. Cyclopropene fatty acids (CPFA) were carcinogenic when fed alone at 20 or 55 ppm, and synergistic when fed with AFB1. In contrast, several flavonoid and indole compounds, especially beta-naphthoflavone (beta-NF) and indole-3-carbinol, inhibited the carcinogenic response when fed prior to and along with AFB1. The mechanisms by which some of these dietary factors modulate AFB1 carcinogenesis were investigated. Dietary beta-naphthoflavone was shown to substantially induce the levels of mixed function oxidase (MFO) activities assayed in vitro. These changes were accompanied by alterations in AFB1 metabolism and binding in freshly isolated hepatocytes. AFB1 incubated in hepatocytes freshly isolated from fish fed beta-NF diet was metabolized more rapidly, showed enhanced rates of detoxication reactions, and decreased accumulation of AFB1-DNA adducts compared to control hepatocytes. These results suggest that beta-NF inhibits AFB1 carcinogenesis at least in part by altering MFO activities such that detoxication is enhanced and initial DNA damage by AFB1 is reduced. In contrast, high dietary protein is a synergist for AFB1 carcinogenesis, and this appears to occur primarily by enhancing the transformation probability for AFB1-initiated genome damage. Fish treated with AFB1 as embryos and then reared on high protein diets had substantially higher incidences of hepatocellular carcinoma (86%) than similarly treated fish fed normal protein diet (44%) or high protein controls without AFB1 exposure (0-2%). The synergistic behavior of dietary CPFAs also appears to partially involve enhanced transformation following DNA damage by AFB1. Fish exposed as embryos to AFB1 and then fed CPFA-containing diets are known to show promotion effects similar to the high protein results (Hendricks, J.D., Proc. 11th Int. Symp. of the Princess Takamatsu Cancer Research Fund, in press.) However, factors other than promotion are involved in the synergism between CPFA and AFB1. Preliminary studies indicate that dietary CPFAs repress MFO activities and depress DNA damage by AFB1 in vitro. If this occurs in vivo, then the net synergistic effect of dietary CPFAs would involve depression of initial AFB1-induced DNA damage, but highly efficient promotion of transformation from the remaining lesions.
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PMID:Mechanisms of dietary modification of aflatoxin B1 carcinogenesis. 681 11

The effect of an antioxidant, disulfiram (DSF), on the carcinogenicities of N-2-fluorenylacetamide (2-FAA) and N-hydroxy-N-2-fluorenylacetamide (N-OH-2-FAA) was examined. DSF given in a diet at a concentration of 0.9% for 1 week before and throughout the carcinogen treatment (0.1 mmol/kg 3 times a week for 4 weeks) reduced the incidence of mammary tumors induced with 2-FAA by 50% and extended the mean latency period of malignant tumors from 5 to 10 months. By contrast, DSF had no effect on mammary carcinogenesis by N-OH-2-FAA. Consistent with these results was the demonstration of the inhibitory effect of DSF on the first step of metabolic activation of 2-FAA, i.e., N-hydroxylation. N-hydroxylation of 2-FAA was significantly inhibited in hepatic microsomes of untreated and 2-FAA-treated male and female rats by DSF given orally. A similar inhibition was shown in vitro after preincubation of hepatic microsomes with DSF. Measurements of cytochrome P450 after pretreatment of rats or microsomes with the inhibition showed no appreciable changes in the hemoprotein content. It was concluded, therefore, that the inhibitory effect of DSF on N-hydroxylation of 2-FAA is accomplished through mechanism(s) other than depression of the cytochrome P450 level. Because both 2-FAA and DSF bind to cytochrome P450 producing a type I spectrum, DSF may interfere with the binding of 2-FAA and thus alter its metabolism.
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PMID:Inhibitory effect of disulfiram on rat mammary tumor induction by N-2-fluorenylacetamide and on its metabolic conversion to N-hydroxy-N-2-fluorenylacetamide. 692 83

Skin cancer, the most common malignancy in white patients, is rare in black populations. Seventeen black patients have been diagnosed and treated for basal cell carcinoma in the past 20 years at the University of Mississippi Medical Center. Ten of them have died, six of various types of cancer. Of the seven living patients, one had two cancers at the time of study: a new basal cell carcinoma and generalized lymphoma. The majority of patients had some degree of mixed racial ancestry, with medium to light brown skin, a history of heavy sun exposure, and lesions appearing on the head or neck. Highly significant depression of cellular immunity was demonstrated in these patients by T-cell assay. Altered tumor surveillance is implied as an etiological factor in basal cell carcinogenesis in black patients.
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PMID:Cellular immune deficiency in black patients with basal cell carcinoma. 696 44

We have reported that a strain of SHR have a selective depression of T-cell functions by aging, which may be due to an early appearance of natural thymocytotoxic autoantibody and a deficiency of thymic hormone. Results presented here showed that the tumor incidence in SHR by low doses of MCA was higher than those in WKA rats with normal T-cell functions. Depression of T-cell functions in SHR could be almost completely restored by allogeneic thymus grafts or injection of extracts from vaccinia virus-infected skin tissues (NSP). When immunological restoration was achieved, generation of killer T-cells against syngeneic tumor cells in SHR was induced and activity of NK cells against K-562 cells was significantly enhanced. Effect of thymus grafts or NSP on MCA-induced primary tumors in SHR was studied. Effect of thymus grafts or NSP on MCA-induced primary tumors in SHR was studied. The tumor incidence was significantly suppressed and average latent periods were also prolonged in SHR grafted with allogeneic thymus. The administration of NSP was not effective on tumor incidence but prolonged latent periods for developments of tumors. From these results, it is suggested that the SHR is a suitable animal model for investigation of role of cell-mediated immunity in carcinogenesis.
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PMID:[Immunological suppression of carcinogenesis in spontaneously hypertensive rats (SHR) with T-cell depression (author's transl)]. 697 36

Numerous studies have indicated that the activities of the polyamine biosynthetic enzymes, ornithine decarboxylase (ODC) and S-adenosyl methionine decarboxylase (SAM.D) are increased in hyperplastic and neoplastic growth. The levels of the polyamines themselves, putrescine, spermidine, and spermine are also often altered in these situations. Epidermal ODC activity is greatly elevated in response to tumor promoting chemicals and also in response to irradiation with short-wave length and mid-wave length ultraviolet. In addition, the levels of the epidermal polyamines change after mid-wavelength ultraviolet irradiation, leading to elevation of putrescine and spermidine, but depression of the spermine level. The spermidine to spermine ratio was significantly elevated after chronic ultraviolet irradiation. Preliminary studies on human skin also shows that mid-wavelength ultraviolet light is capable of inducing ODC. Different pharmacological agents have been found to significantly inhibit the ultraviolet induction of epidermal ODC. Topical corticosteroids and indomethacin significantly inhibit ultraviolet induced opidermal ODC. In addition, retinoic acid inhibited the ultraviolet induction of this enzyme in some experimental situations. Long-wave length ultraviolet alone produced no significant induction of ODC, however, certain phototoxic drugs (8-methoxypsoralen and anthracene) in combination with long-wave length ultraviolet did induce epidermal ODC. It is possible that further studies of changing epidermal polyamine metabolism in response to ultraviolet and tumor promoting agents, may lead to a greater understanding of cutaneous carcinogenesis.
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PMID:Ultraviolet light and epidermal polyamines. 725 49

Tamoxifen was administered in the diet (420 p.p.m.) to female F344 (Fischer), Wistar (LAC-P) and LEW (Lewis) rats to determine for each strain the early morphological and biochemical changes associated with the subsequent development of liver cancer. Hepatic DNA damage, as determined by 32P-postlabelling, showed a cumulative increase with time from 500 adducts/10(8) nucleotides at 30 days to almost 3000 adducts/10(8) nucleotides after 180 days, with little difference between strains at this time point. A significant strain difference was found in the number of adducts present in the Fischer rats at 90 days, compared to the Wistar and Lewis strains. There was a marked strain differences in the time to development of liver tumours. After 6 months treatment, both Wistar and Lewis rats had tumours while none were seen in the Fischer animals. After 11 months, all of the Wistar and Lewis rats had developed liver carcinoma, while the Fischer rats developed liver carcinoma by 20 months. Depression in cell proliferation, relative to age-matched controls, was seen in the livers of Fischer rats after six months of exposure to tamoxifen, in contrast to an increase in the Wistar and Lewis rats. This observation is consistent with the promotion of foci to tumours and the subsequent progression of tumours to carcinomas in the latter two strains. These data may assist in establishing the possible risk factors, such as extent of DNA damage and increased liver cell proliferation, to women with long-term prophylactic exposure to tamoxifen.
Carcinogenesis 1995 Jun
PMID:DNA damage as assessed by 32P-postlabelling in three rat strains exposed to dietary tamoxifen: the relationship between cell proliferation and liver tumour formation. 778 46

Male Fischer rats were maintained for a period of 17 weeks on an iron-deficient diet along with suitable controls. The effect of long term deprivation of iron on xenobiotic metabolism was studied by the activities of various drug metabolising enzymes in both liver as well as extra-hepatic tissues like lungs, kidneys and intestinal mucosa (I.M.). The results show that among the Phase I (activating) enzymes, the hepatic activities of benzo(a)pyrene hydroxylase (AHH) and microsomal epoxide hydrolase (mEH) are significantly reduced in iron deficiency. The other parameters of the activating system, namely cytochrome P450, aminopyrene demethylase (ADM) and aniline hydroxylase (AH), are not altered. Of the two Phase II (conjugating) enzymes studied, only uridine diphospho glucuronyl transferase (UDPGT) is found to be depressed, but not glutathione S-transferase (GST) in liver in iron deficiency. Activities of Phase I enzymes are markedly lowered in extra-hepatic tissues compared to liver; such depression is not observed in conjugating enzymes. Iron deficiency does not seem to make much impact on the enzyme activities of extra-hepatic tissues. Overall, the hepatic results suggest a defect in detoxification mechanisms in iron deficiency. Such impairment may very well predispose an iron-deficient host to an increased risk of carcinogenesis.
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PMID:Effect of long term iron deficiency on the activities of hepatic and extra-hepatic drug metabolising enzymes in Fischer rats. 785 40

The present studies determined the impact of dietary selenite on glutathione homeostasis in liver and mammary tissue and its relationship to biliary excretion of 7,12-dimethylbenz(a)anthracene (DMBA) conjugates. In Experiment 1, liver and mammary tissue concentration of reduced glutathione (GSH) and activities of gamma-glutamylcysteine synthetase (GCS), glutathione reductase (GR) and glutathione S-transferases (GST) were positively correlated with tissue selenium concentration in female rats fed semipurified diets supplemented with sodium selenite (0.05 to 4 mg Se/kg). The magnitude of the response was dependent upon total selenite intake and the tissue examined. Glutathione peroxidase activity did not correlate with tissue GSH concentration. Because both selenite and BHT have been reported to elevate liver GSH, Experiment 2 compared these agents (4 mg Se/kg and 6 g/kg BHT/kg, respectively) on the biliary excretion of DMBA metabolites. Five major biliary DMBA conjugates, three GSH and two beta-glucuronide, were identified. Dietary addition of selenite or BHT enhanced the excretion of these DMBA conjugates by over 100% during the 15-h collection period. These investigations suggest that dietary selenium can alter the concentration of GSH and the activities of three glutathione-dependent enzymes in mammary and liver, accounting for part of the expanded biliary excretion of DMBA conjugates. Enhanced biliary loss of DMBA conjugates likely relates to the reported depression in DMBA binding to mammary cell DNA and the inhibition of DMBA carcinogenesis caused by dietary selenite.
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PMID:Dietary selenite modifies glutathione metabolism and 7,12-dimethylbenz(a)anthracene conjugation in rats. 790 18

Endometrial carcinogenesis induced by concurrent oral administration of ethylenethiourea (ETU) and sodium nitrite (NaNO2) was investigated in ICR (Crj:CD-1) female mice. A mixed solution of ETU (100 mg/kg) and NaNO2 (70 mg/kg) was given to animals orally once a week for up to 6 months and all surviving animals were killed at 12 months of study. During the study, estrous cycle was monitored by vaginal smear and five or 10 selected animals were subjected to interim killing at 3 month interval to observe time-related carcinogenic responses of the uterus. Treatment with ETU and NaNO2 resulted in development of endometrial adenocarcinomas in the uterine horn and the incidence reached 42% in the surviving animals at 12 months. Prior to the development of the tumor, atypical hyperplasia of endometrial glands was frequently observed and regarded as the precancerous lesion. Immunohistochemistry for bromodeoxyuridine (BrdU) incorporation revealed higher labeling indices in both hyperplastic and neoplastic endometrial glandular cells, and the index in the adenocarcinoma was more than 20% on average at any stage of the estrous cycle. Overexpression of p53 protein, which is frequently demonstrated in virulent phenotypes of human corpus cancers, was seen in three out of eight (38%) adenocarcinomas, but not in the atypical hyperplasia or normal endometrial glands. There were no treatment-related changes in the estrous cycle on vaginal smears at any interval of the study. The analyses for plasma ovarian hormones at 12 months disclosed a marked depression of progesterone in the treated animals, while the 17 beta-estradiol (E2) level was comparable to the controls. These results suggest that endometrial carcinogenesis by ETU and NaNO2 could be initiated with atypical hyperplasia of the endometrial gland and a decrease in plasma progesterone level may play an important role in the development of endometrial carcinogenesis. In addition, inactivation of the p53 gene may play a significant role in the malignant transformation of endometrial epithelial cells in mice.
Carcinogenesis 1994 Oct
PMID:Endometrial carcinogenesis induced by concurrent oral administration of ethylenethiourea and sodium nitrite in mice. 795 72

The incidence of cervical cancer is known to decrease with the Westernization of life style. The purpose of this study was to see whether or not the practice of pseudopregnancy conditioning (psp-c) and/or non-Western (rice-rich or rice-and salt-rich) diet conditioning (dt-c) in female mice can reproduce a specific steroidal disorder that is associated with cervical cancer--general depression of androgen and partial depression of corticoid in urine. The effects of psp-c and dt-c were assessed by estimating various steroids in urine and plasma of mice, as collected at the terminal stage of the experiment. Macroscopic and microscopic changes of genital organs were also investigated by dissection. Results obtained are as follows: 1) the practice of psp-c and/or dt-c induced a total of 13 deciduomas in the vagina, the cervix and the corpus of experimental mice. No deciduoma was found in virgin mice fed a standard (Western-style) diet. 2) The combination of 2 reproductive markers (psp-c and non-psp-c) and 3 dietary markers (standard diet, rice-rich diet and rice- and salt-rich diet) produced a variety of changes in the excretions of all androgens, progestins and corticoids in the urine of mice for each of 5 experimental groups. A common steroidal trait was extracted from the urinary steroid data of 5 experimental groups--general depression of androgens, progestins and majority corticoids relative to tetrahydrocortisol. By the collation test, the combination of psp-c and rice- and salt-rich diet conditioning was found to be the best choice for reproducing the urinary steroid changes specific for cervical cancer. 3) The results of plasma steroid analysis, though not incompatible with the urinary steroid data, were fragmentary and not very informative in this study. The observed resistance of mice to carcinogenic insults together with the possible role of deciduoma in cervical carcinogenesis is discussed in the light of relevant information including the anti-carcinogenic action of vitamin C.
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PMID:Hormonal implication of diet and reproductive activity in the genesis of cervical cancer. 807 49

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