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)

Male F344 rats were fed N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT) for up to 4 wk, then were given the basal diets (Prolab 3200 or AIN-76A) with or without 5% sodium saccharin for up to 100 wk. Eleven transitional cell carcinomas (TCCs), one undifferentiated carcinoma, and two sarcomas of the urinary bladder were examined for the expression of ras gene product, p21, by immunohistochemical staining and western blot analysis. Point mutation in codons 12 or 61 of the Ha-ras genes amplified by polymerase chain reaction was examined by a slot-blot screening procedure using allele-specific oligonucleotide probes. Immunohistochemical staining showed enhanced immunoreactivity with the antibody to ras p21 in seven TCCs and one undifferentiated carcinoma. Western blot analysis showed faster migration of the p21 band in 6 of 11 TCCs. Oligonucleotide hybridization revealed the point mutation in codon 12 of Ha-ras gene (GGA----GTA in 1 TCC) and in codon 61 (CAA----CGA in 5 TCCs and CAA----CTA in 1 TCC). Two mutations in codons 12 and 61 coexisted in one tumor, which were found to be present in different Ha-ras alleles. The incidence of Ha-ras gene mutations were similar in groups treated with (3 of 6) or without (3 of 8) sodium saccharin. These results suggest the involvement of activated Ha-ras gene in rat urinary bladder carcinogenesis induced by FANFT.
Mol Carcinog 1990
PMID:Point mutation in codons 12 and 61 of the Ha-ras gene in rat urinary bladder carcinomas induced by N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide. 220 84

The effect of carbon tetrachloride (CCl4) on aflatoxin B1 (AFB1)-induced enzyme altered hepatic foci has been examined in young male Fischer rats given AIN-76A diet. A single i.p. dose of AFB1 (0.2 mg/kg body wt) was given to rats 24 h after partial hepatectomy. Two weeks later, CCl4 (0.8 ml/kg body wt) was injected i.p. once a week for 9 weeks. Animals were sacrificed 24 h after the last dose of CCl4 and glutathione S-transferase placental form (GST-P) and gamma-glutamyl transpeptidase (GGT) positive hepatic foci were analyzed by immunohistochemical and histochemical methods, respectively. Ten weeks after AFB1 dosing, treatment with CCl4 increased the number of AFB1-induced enzyme altered foci several fold and produced a ten to twenty-fold increase in area and volume. GST-P was more sensitive than GGT in detecting AFB1-induced enzyme altered foci. Treatment with AFB1 or CCl4 produced mild hepatic fibrosis in zones 1 and 3 respectively, whereas both treatments produced severe fibrosis in zones 1 to 3 areas. Treatment with CCl4 after AFB1 dosing lowered hepatic GSH levels by 20% and increased lipid peroxidation by 40%. It appears that CCl4, by being an effective enhancer of AFB1-induced enzyme altered hepatic foci in the rat, may mimic cirrhosis observed in human hepatocellular carcinoma.
Exp Mol Med 1998 Dec 31
PMID:Enhancement of aflatoxin B1-induced enzyme altered hepatic foci in rats by treatment with carbon tetrachloride. 989 47

2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) are two important heterocyclic amines formed in proteinaceous foods during the cooking process. Both PhIP and IQ are carcinogenic in several strains of rats. PhIP induces mammary tumors in female F344 rats, while IQ induces principally mammary and liver tumors in female Sprague-Dawley rats. Both PhIP and IQ are activated enzymatically, first by N-hydroxylation, catalyzed by CYP1A1 and CYP1A2, and subsequently by esterification (O-acetylation or sulfation), to yield DNA adducts. Such DNA adduct formation, and persistence of adducts, is related to initiation of carcinogenesis, while inhibition of this process leads to prevention of carcinogenesis. Indole-3-carbinol (I3C), a constituent of cruciferous vegetables, has chemopreventive properties in various systems; it probably acts by induction of detoxification enzymes. We have examined the effect of dietary I3C on DNA adduct formation by PhIP in female F344 rats and on that by IQ in female Sprague-Dawley rats. In experiment 1, F344 rats were maintained on AIN-76A diet containing 0.1% (w/w) I3C and then given p.o. doses (10 or 50 mg/kg) of PhIP. These doses are known to induce CYP1A1 and CYP1A2. Groups of animals (4/time point) were euthanized 1, 2, 6, and 16 days later, and their blood (for isolation of white blood cells), mammary glands, liver, stomach, small intestine, cecum, colon, heart, lungs, kidneys, and spleen were removed for DNA isolation and quantitation of PhIP-DNA adducts by 32P-postlabeling. PhIP-DNA adduct formation was inhibited (40-100%) by I3C in virtually all organs, including the mammary gland (the target organ), at both doses of PhIP, and at almost all time points. In a second experiment, Sprague-Dawley rats were fed either control AIN-76A diet or this diet containing 0.02% I3C or 0.1% I3C for a total of 42 days. IQ was added to the diets (0.01%, w/w) from day 15 to day 42, after which all rats received diet free of IQ and I3C. Groups of animals (4/time point) were killed on days 43 and 57. In addition to the organs removed in experiment 1, the pancreas, uterus, and ovaries were also removed, and IQ-DNA adducts were quantitated by 32P-postlabeling. Both dietary concentrations of I3C inhibited IQ-DNA adduct formation in most organs (except in lungs, kidneys, and pancreas) on both days 43 and 57; in liver, stomach, mammary gland, and spleen, inhibition was evident only on day 43. Inhibitions ranged from 22.6 to 86.6% with the 0.02% I3C diet and from 32.2 to 89.6% with the 0.1% I3C diet. I3C diets did not affect rate of adduct removal in either experiment. It is concluded that dietary I3C inhibits PhIP- and IQ-DNA adduct formation in both target and nontarget organs of female rats, even with high doses of PhIP when CYP1A1 and CYP1A2, the enzymes responsible for the initial activation (N-hydroxylation) of PhIP, are expected to be induced.
J Biochem Mol Toxicol 1999
PMID:Inhibition of DNA adduct formation of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine and 2-amino-3-methylimidazo[4,5-f]quinoline by dietary indole-3-carbinol in female rats. 1040 57

We evaluated the mechanism of action by the phytoestrogen genistein in the prepubertal rat uterus, when administered pharmacologically or physiologically. Female rats were injected with genistein (500 microg/g body weight), estradiol benzoate (EB) (500 ng/g body weight) or vehicle, dimethylsulfoxide (DMSO), on days 16, 18, and 20 postnatal. In 21-day-old rats, both compounds increased circulating estradiol and decreased progesterone concentrations. Uterine estrogen receptor alpha (ER-alpha) and androgen receptor (AR) proteins were reduced, and progesterone receptors (PR) were increased, as measured by western blot analyses. Immunohistochemistry for ER-alpha was confirmatory. Reverse transcription-polymerase chain reaction (RT-PCR) analyses indicated a decrease in ER-alpha, but not in ER-beta, PR and AR mRNA levels following genistein treatment. In prepubertal rats exposed perinatally to 250 mg genistein per kg AIN-76A diet or 250 microg estradiol per kg diet, uterine ER-alpha, AR, and PR proteins were not altered significantly. We conclude that pharmacologic, but not physiologic concentrations of genistein can modulate sex steroid receptor expression in the rat uterus.
Mol Cell Endocrinol 2001 Feb 28
PMID:Sex steroid receptor regulation by genistein in the prepubertal rat uterus. 1122 85

Lipids, either as membrane components or as fuel, are important nutrients that can affect insulin secretion. The aim of this study was to establish the maximum tolerable amount of fat present in the diet, which does not induce significant alteration in the process of insulin secretion. For that, just-weaned male albino rats (70-90 g body weight) were fed during 6 weeks with diets for growing rodents containing 7% fat (A Group) as recommended by the American Institute of Nutrition-AIN. Two other groups in which the fat content of the diet was increased to reach 10% (B Group) or 13% (C Group) were also included. Insulin release, 86Rb+ and 45Ca2+ Fractional Outflow Rate (FOR) during the process of glucose-induced insulin secretion was determined in perfused islets isolated from these animals. No statistical differences in these parameters were detected between A and B rats. However, in the C group, a lower 86Rb+ FOR was found during the whole experiment and a poor insulin secretory response to glucose stimulus was observed. These results led us to postulate that the maximal limiting amount of total lipids present in the diet that does not impair the process of glucose-induced insulin secretion is 10%. These findings authorize future studies on the interference of different dietary lipid sources, in a content 43% more elevated than that recommended (10% against 7%), on the mechanisms of insulin secretion.
Res Commun Mol Pathol Pharmacol
PMID:Tolerable dietary lipid content that does not alter insulin secretion. 1158 61

In cell culture systems, genistein, a soy-derived isoflavone with chemopreventive and estrogenic effects, enhances cAMP-dependent activation of the most common cystic fibrosis-causing mutation, deltaF508-CFTR, by as much as 20-fold. DeltaF508-CFTR is present in the apical membrane at far lower levels than wild-type CFTR. If genistein can enhance cyclic AMP-dependent activity in vivo, the presence of deltaF508-CFTR, at even a few percent of wild-type levels, might permit genistein to be of therapeutic benefit to cystic fibrosis patients with this mutation. Before determining if oral genistein would be of benefit in mice with a deltaF508 mutation in the murine CFTR gene, a maximal dose of oral genistein with minimal side effects needed to be established. Accordingly, C57Bl/6 mice pups were randomly weaned onto soy-free diet, AIN-76, containing between 0 and 1.0 g/kg genistein and allowed to feed ad libitum for 3 weeks. Genistein had no significant effects on growth rates of either male or female mice. Histology of the lung, heart, kidney, liver, and intestine revealed no significant genistein-dependent changes in morphology. When mice on a 1.0 g/kg of genistein diet were sacrificed in the morning, the mean level of serum genistein was 1.4+/-0.2 micro moles/L. Serum genistein increased during the daylight hours reaching a maximum of 7.5+/-0.6 micro moles/L in the early evening. Our results demonstrate that dietary genistein is not inhibitory to growth or caloric intake and up to 1.0 g/kg ad libitum genistein causes no significant organ specific abnormalities.
Pediatr Pathol Mol Med
PMID:Effects of oral genistein in mice. 1255 93

The purpose of this study was to investigate the effects of altering relative intakes of fat and carbohydrates on serum lipid profiles, hepatic acyl-CoA synthetase (ACS), carnitine palmitoyltransferase-I (CPT-I), and the acetyl-CoA carboxlyase (ACC) mRNA level in Sprague-Dawley rats. For four weeks the rats were fed either an AIN-76 diet or one of its modified diets that were supplemented with 20% beef tallow (high-fat diet, HF) and 66.3% sucrose (high-sucrose diet, HS). The HS group had significantly higher serum triglyceride and total cholesterol concentrations when compared with the other groups. Serum LDL-cholesterol concentrations in the HS and HF groups were significantly higher when compared to the normal diet (ND) group. Serum HDL-cholesterol levels of the ND and HS groups were significantly higher than those of the HF group. The hepatic total lipid level of the HF group was significantly higher than those of other groups; triglyceride levels of the HS and HF groups were significantly higher than those of the ND group. Hepatic ACS mRNA levels of the HF group were significantly higher than those of the ND group. Hepatic CPT-I mRNA levels were higher in the HF group than other groups. Also, ACC mRNA levels in the liver increased in the HF group. In conclusion, changes in the composition of dietary fat and carbohydrates could affect the hepatic ACS, CPT-I, and ACC mRNA levels. These results facilitate our understanding of the coordinated regulation of the ACS, CPT-I, and ACC mRNA levels and will serve to enhance our understanding of the molecular mechanisms that underlie the regulation of fatty acid metabolism.
J Biochem Mol Biol 2003 May 31
PMID:The effects of a high-fat or high-sucrose diet on serum lipid profiles, hepatic acyl-CoA synthetase, carnitine palmitoyltransferase-I, and the acetyl-CoA carboxylase mRNA levels in rats. 1278 88

The metabolic functions of NADP(+)-specific isocitrate dehydrogenase (ID2), which may participate in the production of NADPH and biosynthesis of fatty acids, are not yet clearly understood. Accordingly, the current study investigated the effect of oxalomalate, known as a competitive inhibitor of ID2 in vitro, on lipid metabolism and the cellular defense system in vivo. Male Sprague Dawley rats (3 weeks old) were divided into two groups, fed a pelletized AIN-76 semisynthetic diet for 8 weeks, and injected intraperioneally with either saline or oxalomalate (25 mg/kg BW) dissolved in saline every 2 days. Oxalomalate did not lower the body weight and adipose tissue weight significantly; however, it significantly lower the plasma leptin concentration (p < 0.000), plasma and hepatic triglyceride levels (p < 0.01, p < 0.05), and adipocyte lipoprotein lipase activity (p < 0.01) compared to the control group. Meanwhile, hepatic antioxidant enzyme activities, except for superoxide dismutase activity (p < 0.01), glutathione content, and thiobarbituric acid reactive substances levels were not significantly different between the groups. Therefore, the current data suggests that oxalomalate produces a triglyceride-lowering activity and play a possible inhibitory role in fat accumulation. Furthermore, it was not found to affect the most antioxidative enzyme activities, glutathione content, and thiobarbituric acid reactive substances levels in rats fed normal diet.
J Biochem Mol Toxicol 2003
PMID:Effect of oxalomalate on lipid metabolism and antioxidant defense system in rats. 1459 52

Effects of diets on hepatic aflatoxin B1 (AFB1)- DNA binding and AFB1-induced glutathione S- transferase placental (GST-P) form positive hepatic foci have been examined in young male Fischer rats. Animals were fed either AIN-76A or Purina Chow (PC) diet for 1 wk before AFB1- DNA binding studies in vivo and in vitro. Animals were injected i.p. with AFB1 (1 mug/kg body wt) and 3 days later were given either AIN-76A or PC diet with or without 0.1% phenobarbital (PB) in their drinking water. All animals were sacrificed 10 wks after AFB1 dosing for analysis of AFB1-induced GST-P positive hepatic foci by immunochemistry. Two h after i.p. injection of AFB1, hepatic AFB1-DNA binding in AIN-76A fed rats was twice as much as those in PC fed animals without affecting GSH levels. There was no significant effect of diet on either cytochrome P-450 content, GSH levels or microsomal cytochrome P-450 mediated AFB1-DNA binding to exogenous DNA. There was a 40% increase in cytosolic GSH S-transferase activity with 1-chloro-2,4-dinitrobenzene as a substrate in PC fed animals compared to those given AIN- 76A diet. The number and area of AFB1-induced GST-P positive hepatic foci were twice and fivefold as much in AIN-76A fed compared to those in PC fed rats. The number of AFB1-induced GST-P positive foci was increased 5-10 fold in the presence of PB in both groups. In summary, the present data indicate that feeding of PC diet compared to AIN-76A diet inhibits the initiation phase whereas AIN-76A stimulates the promotion phase of AFB1 hepatocarcinogenesis in rats by inhibiting AFB1-DNA binding and increasing AFB1-induced hepatic foci respectively.
Exp Mol Med 2004 Aug 31
PMID:Effect of diet on aflatoxin B1-DNA binding and aflatoxin B1-induced glutathione S-transferase placental form positive hepatic foci in the rat. 1536 54

The influence of glucose-lysine and glucose-methionine Maillard reaction products (MRPs) on calcium availability was studied in rats and in Caco-2 cells. Equimolar glucose/lysine and glucose/methionine mixtures (40% moisture) were heated (150 degrees C, 30 or 90 min) to prepare samples (GL30, GL90, GM30, and GM90, respectively). For 21 days, the rats were fed the AIN-93G diet (control group) or diets containing separately 3% of the heated mixtures (GL30, GL90, GM30, and GM90 groups, respectively). In the last week of the trial, a calcium balance was performed. On day 21, the animals were sacrificed and their livers and femurs removed for analysis of calcium levels. The GL30 and GM30 samples and the corresponding raw mixtures were used for Caco-2 cells experiments. Fecal excretion of calcium decreased and urinary elimination increased in the GM30 and GM90 groups. In accordance, increased calcium transport in Caco-2 cells was found in the presence of the GM30 sample, compared with the raw sample. Bone calcium concentration was lower among the animals consuming MRP diets, compared with the control group. The possible long-term effects of MRP intake on calcium deposition in the bone should be further studied to ascertain the implications on related diseases.
Mol Nutr Food Res 2005 Jul
PMID:Comparative effects of glucose-lysine versus glucose-methionine Maillard reaction products consumption: in vitro and in vivo calcium availability. 1578 17


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