Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In vivo induction of gamma interferon (IFN-gamma) by sensitization of mice with Mycobacterium bovis strain BCG and subsequent challenge with tuberculin depressed the ability of liver homogenates from treated animals to metabolically activate promutagens. The Ames Salmonella typhimurium revertant assay was used for analyses of metabolic conversion of promutagens by liver homogenates. Relative to the mutant frequencies determined with control liver homogenates, induction of IFN-gamma depressed the abilities of homogenates from treated animals to activate N-acetylaminofluorene (AAF), aflatoxin B1 (AFB1), and benzo[a]pyrene (BP) by 55%, 44% and 95%, respectively. Within 18-24 h of Aroclor 1254 treatment, liver P-450 content had increased 43%, and the relative mutant yields per unit protein for all three promutagens had approximately doubled. In vivo induction of IFN-gamma suppressed the Aroclor 1254-dependent increases in mutagenesis by AAF (63%), AFB1 (90%), and BP (reduced to a level 23% below non-Aroclor 1254 treatment). In all cases, the levels of depression of promutagen activation qualitatively correlated with cytochrome P-450 content and the induction of IFN-gamma.
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PMID:Gamma interferon induction depresses murine hepatic promutagen/procarcinogen activation. 641 4

The effect of inhaled ammonium sulfate on benzo[a]pyrene carcinogenesis in the lungs of Syrian golden hamsters was studied. Exposure to ammonium sulfate at an airborne concentration 20 times average United States ambient levels resulted in a significant depression (p less than 0.05) of benzo[a]pyrene carcinogenesis in the first 6 mo of the study. However, at 2 yr, the termination of the study, there were no differences in cancer incidence between groups receiving benzo[a]pyrene and benzo[a]pyrene plus ammonium sulfate. In addition, at the concentration studied, inhaled ammonium sulfate did not significantly increase the incidence or severity of pneumonitis or pulmonary fibrosis in the hamster. However, this inhalation did increase the incidence of emphysema but not the severity. The decreased incidence of cancer during the first 6 mo of this study in animals receiving both benzo[a]pyrene and ammonium sulfate suggests that interaction between sulfate and benzo[a]pyrene does occur, but is insufficient to afford long-term protection against the development of cancer. No enhancement of carcinogenesis by benzo[a]pyrene occurs in the presence of inhaled sulfate.
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PMID:Effects of inhaled ammonium sulfate on benzo[a]pyrene carcinogenesis. 650 34

A single treatment to rats of a low dose of benzo(a)pyrene within 24 hr after birth or at 3 weeks of age accounted for a considerable depression of the binding capacity of glucocorticoid receptors for dexamethasone at 4 months of age. The influence of pretreatment with benzo(a)pyrene was greater in the growing than in the neonatal age. Since the applied treatment did not alter receptor affinity, the decrease in binding capacity was in all probability due to a benzo(a)pyrene-induced decrease in the number of receptors.
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PMID:Effect of benzo(a)pyrene treatment of neonatal and growing rats on steroid receptor binding capacity in adulthood. 652 67

This paper describes the effects of the interferon inducing agents tilorone and polyriboinosinic acid . polyribocytidylic acid (poly IC) on the postnatal development of hepatic cytochrome P-450-linked monooxygenase systems of male rats from birth through early adolescence. The administration of tilorone to rats on days 1 and 2 postpartum modified the changes in the activities of hepatic monooxygenase systems that occur normally during the first four days postpartum. Thus, aniline hydroxylase activity, which develops very rapidly during the first 2 days postpartum, was depressed markedly by tilorone, ethylmorphine N-demethylase activity was depressed moderately, and benzo[a] pyrene hydroxylase, normally the slowest of the three monooxygenase activities to develop, was induced. These changes in monooxygenase activities occurred without a significant change in the cytochrome P-450 content. These observations suggest that not all species of neonatal cytochrome P-450 are affected equally by tilorone administration. By day 7 postpartum, the cytochrome P-450 content and all three monooxygenase activities were depressed in rats that had received tilorone on days 1 and 2 postpartum. All three monooxygenase systems were depressed by the administration of a single dose of poly IC (10 mg/kg) in 1-, 2-, 21-, 28- and 56-day-old rats. The length of the period between maximal depression and complete recovery of cytochrome P-450 systems was shown to be a function of the age of the rat; it increased from about 6 hr in 1-day-old rats to 48 hr in 56-day-old rats. Protein is synthesized more rapidly and degraded more slowly in neonate than in adult animals; this may account for the more rapid recovery of poly IC-induced depression of monooxygenase systems in neonates.
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PMID:Effects of the interferon inducing agents tilorone and polyriboinosinic acid . polyribocytidylic acid (poly IC) on the hepatic monooxygenase systems of the developing neonatal rat. 671 32

The levels of cytochrome P-450, cytochrome b5, aminopyrine N-demethylase, and benzo[a]pyrene hydroxylase were depressed in hepatic microsomes following treatment of mice with the interferon inducer poly rI.rC. The decrease in the hepatic mixed function oxidase system was accompanied by an increase in the incorporation of amino acids into total microsomal protein. Fractionation of solubilized microsomes using a Sephacryl S-200 gel filtration column demonstrated that the increase in amino acid incorporation tended to be associated with proteins with molecular weights under 67 000. The fractions which contained cytochrome P-450 were further separated using a DEAE cellulose column. The amount of labelled amino acids associated with the cytochrome P-450 fractions was uniformly depressed in preparations from poly rI.rC treated animals compared with saline-treated controls. These results suggest that poly rI.rC causes a depression in the rate of synthesis of the apoprotein of cytochrome P-450 while increasing the incorporation of amino acids into other hepatic proteins. The decrease in apocytochrome P-450 synthesis explains the marked loss of drug biotransformation which occurs following induction of interferon.
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PMID:Inhibition of the synthesis of hepatic cytochrome P-450 by the interferon-inducing agent poly rI.rCi. 673 84

The effects of the PCBs mixture, Aroclor 1254, as modifiers of monooxygenases were studied in rabbits and mice. From data presented, it is not possible to generalize the biological effects of PCBs observed with rats, namely, that they are potent, nonspecific inducers of monooxygenase activities. This environmental pollutant enhanced microsomal drug-metabolizing enzymes in livers of rabbits and C57Bl/6J and DBA/2J mice. In rabbit lung, it inhibited, and in rabbit kidney, it enhanced the metabolism of ethylmorphine. Further, at dosages used, PCBs were poor inducers of aryl (benzo(a)pyrene) hydroxylase activity in livers of C57BL/6J and DBA/2J mice; they enhanced aryl hydrocarbon hydroxylase activity in rabbit kidney but caused a significant depression of its activity in rabbit lung. These studies demonstrate that the biologic impact of the widely distributed environmental pollutant, PCBs, may differ in different species and emphasize the need to carry out toxicological studies in more than one species of animals. The differential effects observed on various organs may also be important determinants of organ-targeted chemical toxicity.
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PMID:Polychlorinated biphenyls (PCBs) inducible monooxygenases in rabbits and mice: species and organ specificities. 680 95

Various parameters of haem and drug metabolism were measured during the course of liver regeneration after two-thirds hepatectomy. Partial hepatectomy produced a significant depression in delta-ALA synthetase and delta-ALA dehydratase, and induction in haem oxygenase at an early stage of regeneration. The values returned to normal within 7-14 days. These changes were also accompanied by a marked decline in benzo(a)pyrene hydroxylase and aminopyrene demethylase. The level of glutathione and the activity of glutathione reductase also increased during the early stage of proliferation. The increased level of glutathione with concomitant decrease in drug-metabolizing enzymes and induction in haem oxygenase could be considered as a protective mechanism for the detoxication process, although a contribution from other biotransforming mechanisms cannot be excluded.
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PMID:Haem and drug-metabolizing enzymes in regenerating rat liver. 689 99

The Ah locus represents a complex "cluster" of genese controlling the induction of numerous drug-metabolizing enzyme "activities" by polycyclic aromatic compounds. Allelic differences at the Ah locus are reflected in the large differences in inducibility of cytochrome P1-450 and benzo[a]pyrene metabolism in numerous tissues when the mice receive the chemical daily in their diet. This experimental model system offers to the hematologist and clinical pharmacologist a means to study genetic differences in toxic chemical depression of the bone marrow, as well as a potential model to study aplastic anemia and leukemia explainable on a single-gene basis. The genetically "responsive" individual who is at increased risk for cancer caused by subcutaneous or topical or intratracheal polycyclic hydrocarbons is at decreased risk for toxicity of the bone marrow and leukemia caused by oral benzo[a]pyrene (when compared with the genetically "nonresponsive" individual receiving the same dose of the same xenobiotic). In other words, tissue sites in direct contact with the carcinogen develop cancer in responsive animals because of induced P1-450; tissues in distant sites of the body may develop malignancy in nonresponsive animals because more carcinogen reaches that tissue due to decreased P1-450 induction all over the body and therefore decreased detoxication. Not only the dct with the carcinogen develop cancer in responsive animals because of induced P1-450; tissues in distant sites of the body may develop malignancy in nonresponsive animals because more carcinogen reaches that tissue due to decreased P1-450 induction all over the body and therefore decreased detoxication. Not only the dct with the carcinogen develop cancer in responsive animals because of induced P1-450; tissues in distant sites of the body may develop malignancy in nonresponsive animals because more carcinogen reaches that tissue due to decreased P1-450 induction all over the body and therefore decreased detoxication. Not only the dose but the route of administration and the tissue in which the malignancy or toxicity develops are therefore very important in the interpretation of data from tumorigenesis or toxicity experiments involving P1-450 inducers such as polycyclic hydrocarbons. There exists sufficient evidence that heritable variation of the Ah locus occurs in man. Growing evidence indicates that persons with higher aryl hydrocarbon hydroxylase inducibility in their cultured mitogen-activated lymphocytes may have a statistically significantly increased risk for certain types of cancer and drug toxicity. It remains to be determined at the present time, however, whether this genotype can be used as a biochemical marker in the individual patient for predicting increased susceptibility to certain types of environmentally caused cancers or toxicity in man.
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PMID:Genetic differences in susceptibility to chemically induced myelotoxicity and leukemia. 701 19

Early exposure to benzo(a)pyrene, B(a(P, produces long-lasting effects on the cytochrome P-450 dependent monooxygenase system of rat liver microsomes. Adult male offspring of rats given B(a(P, 20 mg/kg i.p. during late pregnancy, showed either a small but significant depression of basal aryl hydrocarbon hydroxylase acitivity or an impaired induction response to B(a)P. Few significant changes were found in the relative amounts of the individual metabolites formed from B(a)P by microsomes from perinatally exposed rats, either in the basal or B(a)P-induced state. In addition, perinatal exposure to B(a)P tended to decrease the binding of B(a)P to calf thymus DNA in in vitro incubations.
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PMID:Effects of perinatal exposure to benzo(a)pyrene on the aryl hydrocarbon hydroxylase system of adult rat liver. 741 8

The level of 8-OH-2-deoxyguanosine in rat liver DNA was measured as an index of oxidative damage after treating rats for 10 days at a dose ranging from 0.75 to 10 mg/kg with a mixture of 15 pesticides (dithiocarbamate, benomyl, thiabendazole, diphenylamine, chlorthalonil, procimidone, methidathion, chlorpyrifos-ethyl, fenarimol, parathion-methyl, chlorpropham, parathion, vinclozolin, chlorfenvinphos, pirimiphos-ethyl) commonly found in foods of central Italy. At the doses of 0.75 and 1 mg/kg DNA levels of 8-OH-2-deoxyguanosine were significantly increased relative to controls, whereas at higher doses (2.5, 5, 10 mg/kg) the levels returned to control values. The administration of the pesticide mixture dose dependently reduced benzo(a)pyrene hydroxylase, N-demethylase activities, glutathione peroxidase, glutathione reductase, glutathione-S-transferase and thiol transferase activities in the liver. The results show that the pesticide mixture induced free radical DNA damage at low doses. However, at higher doses it produced a depression of cellular metabolism, inhibiting a further expression of oxidative damage.
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PMID:Effect of a mixture of 15 commonly used pesticides on DNA levels of 8-hydroxy-2-deoxyguanosine and xenobiotic metabolizing enzymes in rat liver. 772 83


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