Search PubMed⌕ Search

Biomedical subjects

E Suzuki

Publications and source records attributed to E Suzuki.

At least 433 records · Page 24Linked to original sources
PubMed1985

Metabolic fate of omega-1 and omega-2 oxidized N-nitrosodibutylamines in the rat.

Of the three metabolic oxidation pathways of N-nitrosodibutylamine (NDBA) demonstrated in vivo, omega oxidation is responsible for the induction of bladder tumors, while omega-1 and omega-2 oxidations are considered to be associated with the induction of liver tumors by NDBA. The metabolic fate of the following five NDBA derivatives was investigated in the rat in order to elucidate further the metabolic characteristics of NDBA in relation to its hepatocarcinogenic activity: N-nitroso-N-(3-hydroxybutyl)butylamine (NHBBA-3), N-nitroso-N-(3-oxobutyl)butylamine (NOBBA-3), N-nitroso-N-(2-hydroxybutyl)butylamine (NHBBA-2) and N-nitroso-N-(2-oxobutyl)butylamine (NOBBA-2), which are involved in the omega-1 and omega-2 oxidation pathways of NDBA, and N-nitroso-N-(2-oxopropyl)butylamine (NOPBA), a minor urinary metabolite of NDBA. By characterization of the urinary metabolites, NHBBA-3 and NHBBA-2, primary metabolites of NDBA, were shown to undergo further oxidative metabolic transformation via NOBBA-3 and NOBBA-2, respectively, although conjugation with glucuronic acid to afford the glucuronides was demonstrated to be their principal metabolic pathway. The principal urinary metabolite of NOBBA-2 as well as NOBBA-3 was N-nitroso-N-(carboxymethyl)butylamine, while reduction of the oxo group followed by glucuronidation was found to be a minor metabolic pathway. The glucuronide of N-nitroso-N-(2-hydroxypropyl)butylamine was the principal metabolite of NOPBA, N-nitroso-N-(carboxymethyl)butylamine being a secondary metabolite. The hepatocarcinogenic activity of the three oxo compounds (NOBBA-3, NOBBA-2 and NOPBA) in relation to that of NDBA is discussed from the metabolic point of view.

Animals↗
PubMed1985

Alpha-hydroxylation and mutagenicity of unsymmetrical N-nitrosodialkylamines with a butyl group.

In order to compare the extents of metabolic alpha-hydroxylation of the two alkyl groups in unsymmetrical N-nitrosodialkylamines, N-nitroso-N-alkylbutylamines (alkyl = methyl, ethyl, propyl, butyl, and amyl) were incubated with liver microsomes prepared from phenobarbital- or polychlorinated biphenyl (PCB)-treated and untreated rats, and aldehydes produced by the alpha-hydroxylation were determined quantitatively. Although an increased production of aldehydes was observed with the induced microsomes compared with the non-induced microsomes, no marked differences were noted between the two alkyl groups of these unsymmetric nitrosodialkylamines in regard to the extent of alpha-hydroxylation with the exception of N-nitroso-N-methylbutylamine (NMBA). The amount of aldehydes produced from these nitrosamines increased with elongation of the alkyl chain, amounting to 10-30% of the compounds incubated, and the recovery in the incubation (total aldehyde + nitrosamine recovered) was found to be more than 90%, indicating that alpha-hydroxylation is the principal oxidative metabolic pathway of the nitrosamines in vitro. The microsomal alpha-hydroxylation was inhibited by dimethyl sulfoxide and the extent of the hydroxylation was shown to be positively correlated with the mutagenic potency of the nitrosamines. Based on the mutagenic behavior of NMBA tested on Salmonella typhimurium TA1535 and Escherichia coli WP2 hcr- and the extent of the formation of formaldehyde and butyraldehyde from NMBA in the presence of the induced microsomes and S9 mix, it was concluded that NMBA acts as both a methylating and a butylating agent.

Animals↗
PubMed1984

Carbohydrates as antigenic determinants of tumor-associated antigens recognized by monoclonal anti-tumor antibodies produced in a syngeneic system.

Two monoclonal antibodies (KH-1 and KH-2) against a transplanted fibrosarcoma (KMT-17) in WKA rats were produced by fusing a mouse myeloma (P3-X63-Ag8.653) with spleen cells from syngeneic rats hyperimmunized with KMT-17. Both antibodies showed complement-dependent cytotoxicity against KMT-17. By absorption of cytotoxicity, KH-1 reacted with homologous tumor, other syngeneic fibrosarcomas (KMT-80 and KMT-75), and lung and kidney from normal rats. However, KH-2 reacted with many kinds of tumors and various normal tissues. Antigen specificity was tested by complement fixation and/or solid-phase radioimmunoassay using glycolipids isolated from KMT-17 cells and authentic glycolipids. KH-1 reacted with globotriglycosyl ceramide which was not detected on KMT-17 cells and in cross-reacted weakly with IV3-alpha-galactosyl-lactoneotetraglycosyl ceramide, one of the major glycolipids of KMT-17. The immune reaction was inhibited by alpha-methyl-galactose. KH-2 reacted with lactosyl ceramide and lactoneotetraglycosyl ceramide. The reaction was more potently inhibited by lactose than by beta-methyl-galactose. Antibodies with similar specificity to either KH-1 or KH-2 were elevated in syngeneic rat sera after serial immunization with viable KMT-17 cells.

Animals↗
PubMed1984

Structure-activity relationships of nitrosamines and nitramines which stimulate UDP-glucuronosyltransferase activities in vitro.

Examination of twelve nitrosamines and seven nitramines revealed that nitramines modify UDP-glucuronosyltransferase activity in a manner similar to that of nitrosamines. Only N,N-diethyl-substituted nitrosamine and nitramine significantly stimulated transferase activity toward 2-aminophenol and 4-nitrophenol but not toward phenolphthalein and androsterone. Elongation of the alkyl chains or introduction of carboxy, hydroxy, or oxo groups into the alkyl chains did not result in stimulatory ability, and some of these compounds inhibited the transferase activity.

Aminophenols↗
PubMed1984

Mutagenicity of alpha-hydroxy N-nitrosamines in V79 Chinese hamster cells.

Carcinogenic and mutagenic N-nitrosodialkylamines are metabolically activated through alpha-hydroxylation. The synthesis, chemical properties, and microbial mutagenicity of alpha-hydroxy N-nitrosamines have been reported previously. Potent mutagenicity of four N-nitroso-N-(hydroxymethyl)-alkylamines (alkyl = methyl, ethyl, propyl, and butyl) was demonstrated in the present study in V79 Chinese hamster cells, ouabain resistance being used as an indicator. All the compounds were strong mutagens in the absence of metabolic activation systems. The mutagenic and cytotoxic potencies correlated well with each other, and depended on the alkyl group, decreasing in potency in the following order: methyl greater than ethyl greater than propyl = butyl. Their alkylating reactivity was measured by alkylation of thiophenol, and a good linear relationship was observed between the mutagenic and cytotoxic potencies and their alkylating reactivity. The mutagenic and cytotoxic potencies of the alpha-hydroxy N-nitrosamines in V79 cells were well correlated with those of alpha-acetoxy and alpha-hydroperoxy N-nitrosamines with respect to the effect of alkyl group. The results obtained here supported further that alpha-hydroxy N-nitrosamine is the active species in the metabolic activation of N-nitrosodialkylamine.

Alkylating Agents↗
PubMed1984

Isolation of murine rotavirus in cell cultures. Brief report.

Murine rotavirus was isolated in primary monkey kidney cells. Electrophoretic pattern of genome RNA of murine rotavirus was different from that of human rotaviruses. Oral administration of cultured murine rotavirus caused mild diarrhea in newborn BALB/C mice.

Animals↗
PubMed1984

Heterophile antibodies to rabbit erythrocytes in human sera and identification of the antigen as a glycolipid.

Normal human sera contain heterophile hemagglutinins to rabbit erythrocytes which are different from anti-B isoantibody and other heterophile antibodies such as Hanganutziu-Deicher antibody or Paul-Bunnell antibody. The antigen to this antibody was purified from rabbit erythrocyte stroma, and identified as pentaglycosyl ceramide, Gal(alpha 1-3)Gal(beta 1-4)GlcNAc(beta 1-3)Gal(beta 1-4)Glc-Cer.

Animals↗
PubMed1984

Ten years-long survey on pathogen status of mouse and rat breeding colonies.

Eleven pathogens including P. aeruginosa, Salmonella spp., E. coli O115a, c: K(B), P. pneumotropica, B. bronchiseptica, C. kutscheri, Tyzzer's organism, M. pulmonis, Sendai virus, MHV and Syphacia spp. were surveyed in 217 mouse and rat breeding colonies during 1972-1981. In conventional animals, P. pneumotropica and/or Syphacia spp. were detected in nearly 90% of 89 mouse and 64 rat colonies. Sendai virus, M. pulmonis, P. aeruginosa and MHV were positive in 51.7 to 23.6% of the colonies, and Tyzzer's organism, B. bronchiseptica and probably SDA virus were also detected in more than 10% of the rat colonies. Salmonella spp., E. coli O115a, c: K(B) and C. kutscheri were found in a few colonies. In SPF animals, P. aeruginosa was isolated from about one third of 33 mouse and 31 rat colonies, and P. aeruginosa was isolated from about one third of 33 mouse and 31 rat colonies, and P. pneumotropica was also positive in 3 rat colonies. Infection rates of P. pneumotropica, M. pulmonis, Sendai virus and Syphacia spp. were usually higher than 40% of animals sampled from colonies contaminated with them. Accidental contaminations of SPF colonies were usually caused by P. pneumotropica and Syphacia spp.

Animals↗
PubMed1984

Metabolism of N-nitrodialkylamines.

The in-vitro and in-vivo metabolism of N-nitramines was investigated to compare it with that of N-nitrosamines. N-Nitrodibutylamine and N-nitrodiethylamine were incubated with rat liver microsomes and hepatocytes, and the products were analysed by high-performance liquid chromatography and gas-liquid chromatography. The in-vitro metabolic pattern of these N-nitramines was similar to that of the corresponding N-nitrosamines, except that N-nitromonoalkylamines (produced by alpha-hydroxylation) were isolated and identified after incubation of N-nitrodialkylamines. Seven N-nitramines, including glucuronides, were isolated and identified from urine of rats given N-nitrodibutylamine, produced by omega, omega-1, and alpha oxidations of the N-nitramine. The in-vivo metabolic pattern of N-nitrodibutylamine was also similar to that of N-nitrosodi-n-butylamine except that N-nitromonobutylamine (a product of alpha-hydroxylation) was isolated and identified. N-Nitramines were mutagenic to Escherichia coli WP2 hcr-, but not to Salmonella typhimurium TA 1535. N-Nitrodibutylamine and N-nitrodiethylamine were mutagenic only in the presence of hepatic microsomes, while N-nitromonobutylamine and N-nitromonoethylamine were direct mutagens. Thus, the N-nitrodialkylamine is also metabolically activated to a mutagen through an alpha-hydroxylation.

Animals↗
PubMed1984

Mutagenicity of alpha-hydroxy N-nitrosamines in V79 Chinese hamster cells.

N-Nitrosodialkylamines are activated metabolically by alpha-hydroxylation. Chemical properties and bacterial mutagenicity of alpha-hydroxy N-nitrosamines have been reported previously. This paper describes potent and direct mutagenicity of four N-nitroso-N-(hydroxymethyl)alkylamines in V79 Chinese hamster cells, using ouabain resistance as an indicator. The mutagenic potency depended on the alkyl group, decreasing in the following order: methyl greater than ethyl greater than propyl, butyl. A similar order was observed for cytotoxicity. Mutagenic and cytotoxic potencies of these alpha-hydroxy N-nitrosamines in V79 cells were well correlated not only with those of model compounds (alpha-acetoxy and alpha-hydroperoxy N-nitrosamines), but also with their alkylating ability, measured by alkylation of thiophenol. The mutagenic activity of the alpha-hydroxy N-nitrosamines in V79 cells was shown to be parallel to that in Salmonella typhimurium TA1535 and to that of N-nitrosodialkylamines in V79 cells, after metabolic activation by rat hepatocytes. The results obtained here further support the conclusion that the alpha-hydroxy N-nitrosamine is the active species in the metabolic activation of carcinogenic and mutagenic N-nitrosodialkylamines.

Animals↗