Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Three genotoxic carcinogens and eight tumor promoters were tested for induction of aneuploidy, specifically chromosome loss, in Saccharomyces cerevisiae D61.M. This is a heterozygous diploid yeast strain that permits the scoring of segregants expressing three linked recessive markers (cyhR2, ade6, and leu1), two of which (ade6 and leu1) are located close to the centromere on opposite arms of chromosome VII. The centromere marker leu was routinely checked, and a positive control (bavistan) was run with every experiment. The three genotoxic carcinogens aflatoxin B1, benzo(a)pyrene, and 7,12-dimethylbenz(a)anthracene did not induce aneuploidy, independent of the presence or absence of an exogenous metabolic activation system (rat liver homogenate; S9). Four of the eight tumor promoters tested induced chromosome loss but not mitotic recombination or mutation: cholic acid, lithocholic acid, phenobarbital, and saccharin. Diethylstilbestrol (DES) led to positive as well as to negative results in several independent experiments. In the case of the positive experiment, DES also induced putative recombinants. Three tumor promoters induced neither chromosome loss nor mitotic recombination: anthralin, 4,4'-dichloro-diphenyl-ethane (DDT) and gamma-hexachlorcyclohexane (lindane). From our experiments it can be concluded that the hypothesis put forward by Parry et al. [Nature; 294:263-265], according to which tumor promoters induce chromosome loss in yeast, is not correct in a general sense. In our set of eight tumor promoters, only one half distinctly induced chromosome loss.
Environ Mol Mutagen 1988
PMID:Induction of mitotic chromosome loss in the diploid yeast Saccharomyces cerevisiae D61.M by genotoxic carcinogens and tumor promoters. 328 49

The radiation-sensitive rad mutants of the yeast Saccharomyces cerevisiae exhibit a complex pattern of sensitivity to simple monofunctional alkylating agents. The RAD1, RAD2, RAD4 and RAD14 genes of the RAD3 epistasis group are implicated in the repair of ethylations to DNA. The RAD3, RAD10 and RAD16 genes of this group are not involved. The RAD4 and RAD14 genes have a particular role in repair following exposure to those ethylating agents that preferentially alkylate oxygen, but not to those that preferentially ethylate nitrogen. The RAD1 and RAD2 genes are involved in the repair of damage induced by all the ethylating agents used except EMS. The mutants in this group that are sensitive to ENU were not sensitive to MNU, suggesting that nucleotide excision operates on ethylations but not on methylations. In the RAD6 group, the RAD6 and RAD18 genes are involved in DNA repair after exposure to all the alkylating agents tested, whereas RAD8 appears to have a role in the repair of O-alkylations but not N-alkylations. RAD9 operates in the repair of methylations and ethylations, but does not influence events after exposure to EMS. In the RAD52 group, the mutants tested were sensitive to ENU and DES. Thus some members of all three epistasis groups are involved in the repair of alkylations to DNA.
Mol Gen Genet 1987 Aug
PMID:A complex pattern of sensitivity to simple monofunctional alkylating agents exists amongst the rad mutants of Saccharomyces cerevisiae. 331 52

The conversion of androstenedione (A) to estrogens, testosterone (T) and 5 alpha-reduced metabolites was studied in different phases of cell growth in 4 lines of cultured human breast carcinoma cells. Aromatase activity was 10-fold greater in MD and DM than in MCF7 cells and was undetectable in ZR75 cells. Estrogen formation in MD and DM lines increased during the phase of exponential growth and decreased to 20% of maximum during confluence. 5 alpha-Reductase activity was determined by the formation of 5 alpha-androstane-3,17-dione (5 alpha-A-dione) and androsterone (AND), and was 5-fold greater in ZR75 cells than MD cells and 2-fold greater than in MCF7 cells. This activity was relatively constant during exponential growth and decreased during confluence. T accumulation was inversely related to 5 alpha-reductase activity. The MCF7 and ZR75 cells which contain estrogen receptors had the highest levels of 5 alpha-reductase activity while the MD line which lacks estrogen receptors had the lowest 5 alpha-reductase activity. The assessment of aromatase and 5 alpha-reductase activity in addition to estrogen and progesterone receptors may be helpful in predicting hormone sensitivity in human breast tumours.
Mol Cell Endocrinol 1985 Jul
PMID:The relationship between growth and androstenedione metabolism in four cell lines of human breast carcinoma cells in culture. 386 Apr 51

We investigated the effects of estrogens on the regulation of dopamine receptors in the MtT/W15 transplantable rat pituitary tumor. Diethylstilbestrol (DES) and 17beta-estradiol treatment in female rats significantly decreased the number of dopamine binding sites (B max) from 85 +/- 3.9 fmol/mg protein in untreated rats to 9.2 +/- 1.2 and 8.2 +/- 2.8 fmol/mg protein in DES and 17beta-estradiol-treated rats, respectively, while the binding affinities (Kd) did not change significantly. Testosterone treatment did not change the B max, while ovariectomy resulted in a significant increase in the B max (146.3 +/- 6.7 fmol/mg protein). The effects of DES on the B max were reversible, since removal of the DES for one week before sacrificing the animals led to a marked increase in the B max (54.9 +/- 3.1 fmol/mg protein). Pituitaries from normal female rats treated with DES for 6 and 9 weeks had a significant decrease in the B max. These results show that the number of dopamine binding sites in the membranes of MtT/W15 tumors is decreased by estrogen treatment and that this effect is reversible after removal of the estrogenic stimulus.
Mol Cell Endocrinol 1986 Feb
PMID:Regulation of dopamine receptors in the MtT/W15 transplantable pituitary tumor by estrogen. 394 67

Estrogen (E) induction of riboflavin carrier protein (RCP) in the chicken oviduct and liver was investigated to compare and contrast the kinetics, hormonal specificity and modulation of its elaboration in the 2 steroid-responsive tissues. During primary stimulation, continued daily E administration to immature female chicks elicited, after an initial lag, rapid growth and RCP content of the overduct; neither progesterone (P) nor testosterone (T) could substitute for E in this respect. Furthermore, P given along with E curtailed tissue growth and its RCP content, whereas E + T had a synergistic effect on tissue growth only. During secondary stimulation, E administration steeply enhanced both tissue weight and RCP content without any lag. Interestingly, P (but not T) could substitute for E in augmenting magnum RCP concentration to a comparable extent while a concomitant effect on tissue growth was less marked. In contrast, hepatic induction of RCP was absolutely E-specific during both primary and secondary stimulations. Secondary stimulation with either E or P of E-primed birds enhanced the rates of RCP synthesis in the oviduct relative to that of total protein, whereas in the liver only E was effective in this regard. The absolute rate of E-induced RCP synthesis in both the steroid-stimulated tissues was significantly higher than that of general protein elaboration.
Mol Cell Endocrinol 1986 Mar
PMID:Hormonal induction of riboflavin carrier protein in the chicken oviduct and liver: a comparison of kinetics and modulation. 395 57

Ovariectomy or ovariohysterectomy on day 18 of pregnancy augmented mammary beta-casein content 28 h later. Progesterone injected immediately and 12 h after ovariectomy showed a clear inhibitory effect on casein synthesis. Estrogen induced a significant increase in mammary beta-casein content when injected 12 h after surgery. Treatment with CB-154 to prevent prolactin release did not affect the increase of casein induced by ovariectomy. When CB-154 was injected to ovariohysterectomized pregnant rats, significant reduction of casein synthesis was obtained. According to these findings, rat placental lactogen in the absence of prolactin and progesterone induces beta-casein synthesis. Therefore prolactin, ovarian and placental hormones interplay at the end of pregnancy for full expression of the mammary gland genome.
Mol Cell Endocrinol 1985 Feb
PMID:Hormonal regulation of casein synthesis at the end of pregnancy. 397 61

The relative induction of FSH and LH receptors in the granulosa cells of immature rat ovary by pregnant mare serum gonadotropin (PMSG) has been studied. A single injection of PMSG (15 IU) brought about a 3- and 12-fold increase in FSH and LH receptor concentration, respectively, in the granulosa cells. Maximal concentration was reached by 72 h but the receptor levels showed a sharp decline during the next 24-48 h. The kinetic properties of the newly formed FSH receptors were indistinguishable from the pre-existing ones. The induced FSH receptors were functional as demonstrated by an increase in the in vitro responsiveness of the cells to exogenous FSH in terms of progesterone production. Treatment of immature rats with cyanoketone, an inhibitor of delta 5,3 beta-hydroxysteroid dehydrogenase, prior to PMSG injection effectively reduced the PMSG-stimulated increase in the serum estradiol, uterine weight and LH receptors but had no effect on the FSH receptor induction. The ability of PMSG to induce gonadotropin receptors can be arrested at any given time by injecting its antibody, thereby suggesting a continuous need for the hormonal inducer. Estrogen in the absence of the primary inducer was unable to maintain the induced LH and FSH receptor concentration. Inhibition of prostaglandin synthesis using indomethacin aslo had no effect on either the induction or degradation of gonadotropin receptors. Administration of PMSG antiserum, 48 h after PMSG injection, brought about a rapid decline in the induced receptors over the next 24 h, with a rate constant and t 1/2 of 0.078 h-1 and 8.9 h for FSH receptors and 0.086 h-1 and 8.0 h for the LH receptors, respectively.
Mol Cell Endocrinol 1984 Sep
PMID:Effect of pregnant mare serum gonadotropin on the induction and degradation of FSH and LH receptors in the granulosa cell of the immature rat. 609 76

Pregnant mice were injected with 12.5 micrograms DES/kg body weight or 25 micrograms DES/kg body weight daily from gestation day 9 through day 12 or 16 and sacrificed on day 13 or 17. Placentas of DES treated animals were smaller than controls, the effect being dose dependent. Histologic changes in 13 gestation day placentas regional thinning of the labyrinth associated with an apparent inhibition of trophoblast maturation and development of fetal blood vessels. Knots of mononuclear cells form in the labyrinthine region of 13 day placentas exposed to the higher dose of DES. By 17 days gestation, coagulative necrosis is common in the decidua basalis, being most severe in those animals receiving 25 micrograms DES/kg. In many placentas the labyrinthine region is absent. The only remaining elements are trophoblast cells, giant cells and glycogen-containing cells. Fetal deaths associated with the lower dose of DES increased with time whereas 100% fetal mortality was associated with the higher dose.
Virchows Arch B Cell Pathol Incl Mol Pathol 1980
PMID:Placental changes due to administration of diethylstilbestrol (DES). 610 45

Histology, selective histochemistry and electron microscopy were used to examine the ovarian structure of offspring from mice administered DES (10 micrograms/kg in 0.1 cc of corn oil, subcutaneously) or corn oil alone on Day 15 of gestation. Offspring were sacrificed at 7 months of age. Ovarian changes in DES exposed offspring included the absence of distinguishable corpora lutea but the presence of follicles in various stages of growth and atresia. Large accumulations of pigmented cells and numerous enlarged, pale vacuolated interstitial cells were observed. Interstitial cells contained membrane bound vacuoles, lipid droplets and clumped pigmented material. A concentric pattern of membranes was often observed within the pigment. The results indicate that a single exposure to DES on Day 15 of gestation had a dramatic influence on ovarian morphology and function in 7 month old offspring. The ovarian morphology is consistent with tonic release of FSH and LH and failure in ovulation.
Virchows Arch B Cell Pathol Incl Mol Pathol 1984
PMID:Histology and ultrastructure of the adult mouse ovary following a single prenatal exposure to diethylstilbestrol. 614 17

The effect of estrogen on cell proliferation in the descending colon of the mouse as an example of a non-target organ was investigated. Ovariectomized mice were given single or multiple injections of 10 ng/g body weight of 17 beta-estradiol and were killed 1 h after 3H-thymidine injection. Estrogen treatments decreased incorporation of 3H-thymidine into the DNA of colonic mucosa most markedly at 4 h after the single or the last of multiple injections. The inhibitory effect of estrogen on 3H-thymidine incorporation was greater and lasted longer after a single injection than after multiple ones. A similar inhibitory effect was observed in the colonic mucosa of male mice as well as in the mucosa of mice in which colonic epithelial cell proliferation was enhanced by refeeding after 48 h of fasting. However, the colonic mucosa of mice treated with estrogen implants for up to 4 days was not affected. Estrogen treatments caused no significant change in the DNA, RNA and protein contents of the colonic mucosa. The efficacy of estrogen treatments was verified by an increase in both the wet and dry weights of the uterine horns of ovariectomized mice.
Virchows Arch B Cell Pathol Incl Mol Pathol 1981
PMID:Effect of estrogen on cell proliferation in colonic mucosa of the mouse. 616 94


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