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C Negishi

Publications and source records attributed to C Negishi.

At least 37 records · Page 2Linked to original sources
PubMed1993

[P-31 MR spectroscopy of excised pig liver].

This study used P-31 MR spectroscopy (P-31 MRS) to evaluate the viability of a pig liver preserved with perfusate. Pig liver was excised and preserved in cooled Euro-Collins solution after canulation of the portal vein and perfusion with the solution. P-31 MRS was performed on a 1.5 Tesla machine. P-31 MRS showed that the beta-peak of ATP in the preserved pig liver diminished within two hours. P-31 MRS of pig liver with perfusion of cooled and oxygenated Euro-Collins solution revealed a significant increase in the beta-peak in the pig liver preserved 7 hr compared with that preserved for a longer time. Assessing the beta-peak of ATP by P-31 MRS with cooled and oxygenated Euro-Collins solution is valuable to evaluate the viability of preserved pig liver.

Animals↗
PubMed1992

Preclinical evaluation of Gd-EOB-DTPA as a contrast agent in MR imaging of the hepatobiliary system.

Gadolinium diethylenetriaminepentaacetic acid (DTPA) covalently linked to the lipophilic ethoxybenzyl moiety (Gd-EOB-DTPA) was designed for use as a contrast agent in hepatobiliary magnetic resonance imaging. With T1 relaxivity values of 8.7 L/mmol.second in plasma and 16.6 L/mmol.second in rat liver tissue and a median lethal dose of 10 mmol/kg when administered intravenously in mice and rats, Gd-EOB-DTPA has a fairly high margin of safety. In rats and monkeys, biodistribution studies performed 7 days after administration of 0.25 mmol/kg revealed very little retention of gadolinium (less than 1%) in the tissues, indicating complete elimination via renal and biliary excretion. Biliary excretion was inhibited by coadministration of sulfobromophthalein, indicating the involvement of a carrier-mediated transport system based on the enzyme glutathione-S-transferase. In rats, the biliary transport maximum was 5 mumol gadolinium/min.kg. High T1 relaxivity of Gd-EOB-DTPA in rat liver in vivo can be explained by transient interaction with intracellular components and by increased microviscosity inside the hepatocyte.

Animals↗
PubMed1989

Nucleic acid binding and mutagenicity of active metabolites of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline.

2-Amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) is a potent mutagen and carcinogen present in heated foodstuffs. The covalent binding of MeIQx to calf thymus DNA and calf liver RNA with microsomal activation was demonstrated. A major metabolite which exerts a direct mutagenic effect on S. typhimurium TA98 was found by HPLC analysis after incubation of MeIQx with rat liver microsomal fraction. The metabolite was identified as 2-hydroxyamino-3,8-dimethylimidazo[4,5-f]quinoxaline (N-OH-MeIQx). Synthetic N-OH-MeIQx was found to bind non-enzymatically to DNA and RNA at neutral pH even at 0 degrees C. Addition of acetic anhydride increased the binding of N-OH-MeIQx to DNA 10 times. These results suggest that MeIQx is metabolized to N-OH-MeIQx by microsomal cytochrome P-450 and further activated to an acetylated form that binds efficiently to nucleic acids in rat liver. Preferential modification of polyguanylic acid suggests that guanine residues of DNA are mainly modified with MeIQx. Synthetic N-OH-MeIQx exerted direct mutagenic activity on S. typhimurium TA98 inducing 150,000 rev/micrograms. Pentachlorophenol (PCP) caused a dose-dependent inhibition of this mutagenic effect, but 2,6-dichloro-4-nitrophenol (DCNP) did not. Thus the acetyltransferase of S. typhimurium seems to be important for the high mutagenicity of MeIQx after its microsomal activation.

Biotransformation↗
PubMed1986

N-acetyl derivative as the major active metabolite of 2-amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole in rat bile.

2-Amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (Glu-P-1) is a mutagen and carcinogen isolated from a glutamic acid pyrolysate. When this 14C-labeled compound was administered to male F344 rats at a dose of 0.3 mCi (20.8 mg)/kg b.w., 70% of the radioactivity was excreted into the bile in 24 h. On HPLC analysis of this bile, several metabolites of Glu-P-1 were found with unmetabolized Glu-P-1. One of the mutagenic metabolites was identified as N-acetyl-Glu-P-1. This metabolite had a specific mutagenic activity of about one quarter of that of Glu-P-1 and its amount in the bile corresponded to a few percent of the dose of Glu-P-1 administered.

Animals↗
PubMed1986

Metabolic aspects of pyrolysis mutagens in food.

The first step in metabolic activation of mutagenic and carcinogenic heterocyclic amines has been elucidated to be N-hydroxylation by cytochrome P-448. N-Hydroxyamino compounds are further activated to form N-O-acyl derivatives that readily react with DNA. The adducts between the metabolites of Trp-P-2 and Glu-P-1 and DNA were shown to have a C8-guanylamino structure. In the case of Glu-P-1, modification of guanine in GC clusters occurred preferentially. Glutathione transferases and myeloperoxidase were shown to inactivate some heterocyclic amines or their active metabolites. Hemin and fatty acids bind to and inactivate them. Fibers and other factors from vegetables also work to inactivate heterocyclic amines. Nitrite at low pH also degraded some heterocyclic amines, but those with an imidazole moiety were resistant. Glu-P-1 induced intestinal tumors in a high incidence when fed orally to rats. When 14C-Glu-P-1 was administered by gavage into rats about 50% and 35% were excreted into feces and urine, respectively, within 24 hr. When the bile was collected, around 60% of radioactivity was excreted into it within 24 hr. In the bile, N-acetyl-Glu-P-1 was identified as one of the metabolites of Glu-P-1. It showed a mutagenic activity of about one fourth that of Glu-P-1 with S9 mix. Some radioactivity was also detected in the blood. At 24 hr after administration, most of the radioactivity was found to be bound to erythrocyte beta-globins and serum proteins including albumin.

Animals↗
PubMed1986

Presence of albumin-positive cells in the liver of analbuminemic rats and their increase on treatment with hepatocarcinogens.

The analbuminemic rat is a mutant in which albumin mRNA processing is blocked owing to a seven-base-pair deletion in the 9th intron of the albumin gene. A small amount of albumin is detected in the serum of this rat. Production of serum albumin in the liver of this mutant rat was studied by an immunohistochemical method. The results showed that a few albumin-positive cells were present in the liver of the mutant rat, whereas all the hepatocytes in normal rat liver were albumin-positive. In the mutant the number of albumin-positive cells increased with age: their frequency was 10(-5) at birth and 6 X 10(-3) at 45 weeks of age. On administration of 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB) and 2-acetylaminofluorene, albumin-positive cells increased dramatically. Their numbers were 7 to 10 times those of untreated rats after 10 to 16 weeks of carcinogen treatment. The number of albumin-positive cells did not decrease after 3'-Me-DAB feeding was discontinued. In regenerating liver after partial hepatectomy, clusters of albumin-positive cells increased while the number of singlet albumin-positive cells decreased. These observations suggest that the appearance of albumin-positive cells in analbuminemic rat liver may be due to a somatic mutation of the hepatocytes.

2-Acetylaminofluorene↗
PubMed1985

Use of nitrite and hypochlorite treatments in determination of the contributions of IQ-type and non-IQ-type heterocyclic amines to the mutagenicities in crude pyrolyzed materials.

The mutagenic heterocyclic amines Glu-P-2, MeA alpha C and Phe-P-1, which possess a 2-aminopyridine structure in their molecule (non-IQ-type mutagens), were found to be inactivated by nitrite treatment under acidic conditions, as observed previously with Trp-P-1, Trp-P-2, Glu-P-1 and A alpha C. In contrast, MeIQx, 4,8- and 7,8-DiMeIQx, which were originally isolated from fried beef or heated model mixtures of creatinine, amino acids and glucose, and which have a 2-aminoimidazole moiety in their molecules (IQ-type mutagens), were very resistant to nitrite treatment like IQ and MeIQ. Both types of mutagenic heterocyclic amines were completely inactivated by treatment with hypochlorite. This differential inactivation of mutagenic heterocyclic amines by nitrite and hypochlorite was used in determination of the contributions of IQ-type and non-IQ-type mutagens to the total mutagenicities of various pyrolyzed materials. The percentage contributions of IQ-type mutagens to the mutagenicities of broiled sardine, fried beef, broiled horse mackerel, cigarette smoke condensate and albumin tar were 88, 75, 48, 6 and 4, respectively.

Amines↗
PubMed1985

Absence of carcinogenicity of 1-nitropyrene, correction of previous results, and new demonstration of carcinogenicity of 1,6-dinitropyrene in rats.

1-Nitropyrene (1-NP), 1,6-dinitropyrene (1,6-DNP) and 1,8-dinitropyrene (1,8-DNP), which are potent mutagenic components of diesel exhaust and air pollutants, were injected subcutaneously into the back of F344 rats. No tumor was induced by experimental day 650 in rats treated with 40 or 4 mg of 1-NP. On the other hand, 1,6-DNP at a total dose of 4 mg was demonstrated to induce sarcomas at the injection site in all 10 rats. 1,8-DNP at total doses of 0.4 and 0.04 mg also induced sarcomas in 10 and 9 out of 10 rats, respectively, by day 320. Our previous finding that 1-NP was carcinogenic was possibly due to contamination of the preparation with dinitropyrenes.

Animals↗
PubMed1985

Effects of meat composition and cooking conditions on the formation of mutagenic imidazoquinoxalines (MeIQx and its methyl derivatives).

In recent years it has been shown that certain methyl derivatives of 3H-imidazo[4,5-f]quinoxaline-2-amine are responsible for a major part of the mutagenicity formed during frying, broiling or baking of meat, and also formed in the preparation of meat extracts. The present study describes the precursors of these compounds and their formation with participation of Maillard or nonenzymatic browning reactions. The formation of these IQ-type mutagens was shown to occur when model systems of creatin(in)e, reducing monosaccharides, and certain amino acids were heated at 128 degrees C for 2 hr. In meat experiments, the mutagenicity was found to be significantly correlated with the presence of creatin(in)e in the meat samples. The same conditions that are favorable for Maillard reactions, such as supply of starting materials, high temperature, and a suitable water concentration, also increased the yield of mutagenicity during cooking. Fats seemed to act as regulators of the amount of heat transferred into the product rather than as reactants in the formation of mutagenicity.

Amino Acids↗
PubMed1984

Formation of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline in a model system by heating creatinine, glycine and glucose.

A mixture of creatinine, glucose and glycine was heated in diethylene glycol containing 14% water for 2 h at 128 degrees C, and the mutagens formed were purified by XAD-2 column chromatography, acid-base partition, Sephadex LH-20 column chromatography, 'blue cotton' treatment and HPLC. Two mutagenic substances were isolated by HPLC. The major mutagen was identified by its UV absorption and mass and NMR spectra as 2-amino-3,8- dimethylimidazo [4,5-f]quinoxaline, which was originally isolated from fried beef. This finding supported the idea that creatinine, amino acids and sugars present in meat are precursors in the formation of the mutagenic imidazoquinoxaline derivative.

Chemical Phenomena↗
PubMed1984

Induction of sarcomas in rats by subcutaneous injection of dinitropyrenes.

The carcinogenicities of potent mutagenic dinitropyrenes were examined by their subcutaneous injections into male F344/ DuCrj rats. Animals were injected with 0.2 mg each of 1,3- and 1,8-dinitropyrenes (1,3- and 1,8- DNPs ) dissolved in 0.2 ml of dimethyl sulfoxide (DMSO) twice a week for 10 weeks. In rats treated with 1,8-DNP, sarcomas were induced at the sites of injection in all 10 animals tested between the 113th and 127th experimental days. In rats treated with 1,3-DNP, 10 of 10 rats developed sarcomas between days 119 and 320. Some tumors induced by these chemicals were transplantable into the same strain of rats. No tumors developed in control rats, which received only DMSO.

Animals↗
PubMed1983

Variations of 1-deoxyglucose(1,5-anhydroglucitol) content in plasma from patients with insulin-dependent diabetes mellitus.

The concentration of 1-deoxyglucose(1,5-anhydroglucitol) in plasma from patients with insulin-dependent diabetes mellitus was measured by gas-liquid chromatography with an all-glass capillary column. Twenty-one plasma samples were obtained from 21 patients before insulin therapy, and 34 more from 13 patients receiving insulin therapy. 1-Deoxyglucose was generally not detectable in plasmas of diabetic patients before they received insulin; it was measurable in the patients who had received insulin, although its concentration was low compared with that of healthy subjects. We therefore suggest that the absence of 1-deoxyglucose in plasma is one of the markers of metabolic states of diabetes, perhaps reflecting a disturbed function of carbohydrate metabolism; its presence in plasma within a normal range may reflect the better control of diabetic patients.

Blood Glucose↗