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S Arimoto

Publications and source records attributed to S Arimoto.

At least 19 recordsLinked to original sources
PubMed1997

Enhancement of the clastogenicity of N-nitrosodialkylamines plus near-ultraviolet irradiation by ethanol in Chinese hamster lung fibroblasts.

Early work from our laboratory showed a synergistic action of N-nitrosodialkylamines and near-ultraviolet light (UVA, 320-400 nm) to cause mutations in bacteria and phages. Recently we reported that N-nitrosodialkylamines + UVA induces chromosome aberrations in Chinese hamster lung cells in culture. We have now found that ethanol can potentiate this clastogenic action of N-nitrosodialkylamines + UVA. When the cells were treated with N-nitrosopyrrolidine (NPYR) or N-nitrosodiethylamine (NDEA) + UVA for 2 hours in the presence of 1% ethanol, approximately 2-fold increase in the numbers of cells with aberrant chromosomes was observed, compared to those found without the ethanol. NPYR/NDEA only ethanol only, or ethanol + UVA did not cause the aberrations. The enhancement was dependent on the concentration of ethanol. Treatment of cells with ethanol before the NPYR + UVA was ineffective. By contrast, treatment of cells with NPYR-UVA and then with ethanol was as effective as with the simultaneous treatment. Methanol showed synergistic effects similar to those of ethanol, but mannitol did not. Intracellular hydrogen peroxide was found to be increased twofold over that in the background by a treatment with ethanol + UVA. The alcohol-mediated enhancement of the clastogenic action of N-nitrosodialkylamines + UVA may be a consequence of an increase in intracellular oxidative stress, or simply due to increased membrane permeability.

Animals↗
PubMed1996

A short-column technique for concentrating mutagens/carcinogens having polycyclic structures.

Copper phthalocyanine trisulfonate (cpt) is known to form complexes with polycyclic planar compounds and for that reason has been used in a rayon fiber supported form as a ligand to selectively trap polycyclics, e.g., mutagenic/carcinogenic heterocyclic amines and polycyclic hydrocarbons. With the rayon-supported ept, batch-wise treatment is employed in the adsorption of polycyclic mutagens from samples such as an aqueous extract of food, river water, and human urine. We have now found that chitin (poly-N-acetylglucosamine) powder bearing covalently linked cpt residues is suitable for preparing a short packed column through which a sample solution may be passed. The derivatization of chitin to fix the ept ligand on the hydroxyl groups with the use of Reactive Blue 21 proceeded more rapidly than that of the cellulose supports, and the resulting cpt-chitin showed a ept content of 44 mol/g, a content twofold greater than that of cpt-rayon and fourfold greater than that of cpt cellulose prepared under equivalent conditions. A sample of ept-chitin (0.12 g) was placed in a Sep-Pak cartridge case, and the column was tested for its utility. Compounds, mostly mutagens, having structures of three or more fused rings (aflatoxin B1, IQ, PhIP, and six others tested) were efficiently adsorbed (>85%) to the column when their 104106 M buffered solutions (5 ml, pH 7) were passed through it (flow rate, 510 mI/mm). Compounds with fewer than three rings (eight compounds tested) flowed through the column with little or no adsorptions. The adsorbed compounds can be eluted with a mixture of methanol and concentrated ammonia. This technique was successfully applied for concentrating mutagenic components from Beef Extract and river water. The method is superior to the previous methods in terms of selectivity and high recovery for polycyclics. Simplicity and a less time-consuming nature of manipulation are advantageous.

Adsorption↗
PubMed1996

Mutations and oxidative DNA damage in phage M13mp2 exposed to N-nitrosomorpholine plus near-ultraviolet light.

Previously we reported that a direct-acting mutagen can be formed from N-nitrosomorpholine (NMOR) on exposure to near-ultraviolet light (UVA, 320-400 nm). We have now studied the spectrum of mutations caused by NMOR plus UVA. M13mp2 phages suspended in a sodium phosphate buffer were treated with NMOR under UVA irradiation and Escherichia coli NR9099 was then infected with the phage. Mutations induced in the phage DNA lacZ alpha region were analyzed. The majority (approximately 50%) of the induced sequence changes were G to T transversions. This suggested that modifications in guanine residues were responsible for these transversions. We explored the formation of 7,8-dihydro-8-oxodeoxyguanosine (8-oxodG) in the DNA. When the phage were treated with NMOR plus UVA, 8-oxodG/dG in DNA increased up to 12-fold over the value in untreated control. When a mutM-deficient mutant of E. coli CSH50 was used as the host, the mutation level was higher than that observed with CSH50. We conclude that 8-oxodG may be involved in mutations induced by NMOR plus UVA.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1995

Inhibitory effect of hemin, chlorophyllin and related pyrrole pigments on the mutagenicity of benzo[a]pyrene and its metabolites.

Hemin and chlorophyllin are known to inhibit strongly the mutagenicity of benzo[a]pyrene in the Salmonella assay. To further investigate this phenomenon, a series of these pyrrole pigments including pure samples of Cu- and Fe-chlorins were tested for their potency to inhibit the mutagenicity of benzo[a]pyrene and its metabolites, benzo[a]pyrene-7,8-diol, benzo[a]pyrene-4,5-epoxide, and benzo[a]pyrene-7,8-diol-9,10-epoxide. Hemin was the most potent among the pigments tested for these inhibitions. Both hemin and Cu-chlorin accelerated efficiently the degradation of benzo[a]pyrene-7,8-diol-9,10-epoxide, and this acceleration seemed to be the predominant mechanism by which these pigments inhibit the overall mutagenicity of benzo[a]pyrene in Salmonella. Based on spectroscopic evidence, we speculate that a complex formation between hemin and benzo[a]pyrene-7,8-diol-9,10-epoxide takes place and that this complexing is the cause of the accelerated degradation.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1995

Synergistic action of N-nitrosodialkylamines and near-UV in the induction of chromosome aberrations in Chinese hamster lung fibroblasts in vitro.

N-Nitrosodialkylamines are promutagens and proclastogens, requiring metabolic activation for their actions. Previously, we showed that direct-acting bacterial mutagens can be formed from N-nitrosodialkylamines on exposure to near-UV. We have now found that N-nitrosodialkylamines with near-UV irradiation are clastogenic to Chinese hamster lung cells. When the cells in culture were irradiated with near-UV for 3 h in the presence of N-nitrosodimethylamine (NDMA), N-nitrosodiethylamine (NDEA), N-nitrosopyrrolidine (NPYR), N-nitrosopiperidine (NPIP) or N-nitrosomorpholine (NMOR), and then further incubated for a total period of 24 h with the N-nitrosodialkylamines, chromosome aberrations were induced. Neither the N-nitrosodialkylamine nor near-UV alone were clastogenic. Severe clastogenicity (> 50% of cells examined showing aberrations) was observed for 0.5 mM NDEA, NPYR and NPIP. The order of the clastogenic activity was NDEA, NPYR > NPIP, NDMA > NMOR. This order differed from that of bacterial mutagenicity previously reported for these N-nitrosodialkylamines plus near-UV, in which NMOR gave the strongest activity. The chromosome aberrations induced by the NPYR and NDEA plus near-UV in CHL-cells were inhibited by superoxide dismutase, glutathione and L-cysteine. Dimethylsulfoxide or D-mannitol, scavengers of hydroxy radical, and L-histidine, a scavenger of single oxygen, were ineffective. These results suggest that superoxide formed by a synergistic action of an N-nitrosodialkylamine and near-UV is the cause of the chromosome aberrations observed, an assumption consistent with the known ability of superoxide to cleave DNA.

Animals↗
PubMed1994

Retention of a mutagen, 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2), in the liver of mice infected with Schistosoma japonicum.

Regarding the mechanism underlying the suspected enhancement of hepatic cancers among Schistosoma japonicum-infected humans, we hypothesized that mutagen exposures in the livers of patients may be enhanced due to the parasitic infection. To explore this possibility, we have done a model experiment using mice and a carcinogenic mutagen, 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2). Mice infected with Schistosoma japonicum were intravenously administered Trp-P-2, and the mutagenic activities of the mouse serum and of the liver tissue extracts, which were observable during the 6-h period after the administration, were investigated. The level of serum indirect mutagenicity, which probably reflected the amount of unmetabolized Trp-P-2, was higher in the infected animals than in uninfected control animals. Direct mutagenicity in the serum, on the other hand, was higher in the control animals than in the infected mice. Furthermore, the liver tissue extracts from infected mice showed higher indirect-mutagenicity than those from the controls. These data suggest that the infection results in a decreased metabolism and an increased retention of Trp-P-2 in the liver. Consistent with this phenomenon, pigments in the liver formed by the schistosome infection were found to be an efficient adsorbent for Trp-P-2. Thus, the possibility exists that these pigments, which contain hematin as a major constituent, may function as a reservoir for the mutagen, thereby prolonging the exposure period of the liver to the mutagen.

Adsorption↗
PubMed1994

Parasite infection and cancer: with special emphasis on Schistosoma japonicum infections (Trematoda). A review.

This article contains a review of current knowledge on the association of parasite infections and cancer formation, especially that of Schistosoma japonicum (Trematoda) in man and experimental animals. The association of S. haematobium infection and bladder cancer is well known and documented. However, S. japonicum infection has also been reported to be associated with cancer, in this case hepatocellular carcinoma and/or colorectal cancer. Pathological records and analyses have shown a correlation between this infection and cancer, and pathohistological descriptions have been numerous, together with clinical case reports. Epidemiological analyses have been conducted in China and Japan and support a role of S. japonicum infection as one of the risk factors in cancer formation, along with others, such as hepatitis virus infection and alcoholic intake. Experimental results have also shown that cancer appears early and in larger numbers in experimentally infected animals given a known carcinogen. In spite of these positive end-point associations, the mechanism of schistosome-mediated enhancement of carcinogenesis is obscure. A suggestive observation is that in S. japonicum-infected mice carcinogen-metabolizing hepatic activity including P-450 was decreased so that an administered carcinogen persisted for a longer period than in uninfected mice. Further studies, both epidemiological and experimental, are needed to firmly establish the relationship between schistosome infection and cancer.

Animals↗
PubMed1993

Binding of polycyclic planar mutagens to chlorophyllin resulting in inhibition of the mutagenic activity.

Chlorophyllin is known to inhibit the mutagenicity of a variety of compounds. Using highly purified samples of chlorophyllin and its family compounds, we studied the mechanism of the inhibition. Since mutagens with polycyclic planar structures are particularly strongly inhibited, it seemed likely that the inhibition arises by trapping of the mutagens by chlorophyllin through complex formation at the planar surfaces of these molecules. To explore this possibility, we prepared a Sepharose bearing covalently linked chlorophyllin as ligand, and the adsorption of mutagens to this Sepharose was measured. Three different chlorophyllin derivatives were used, i.e., copper-chlorin, iron-chlorin and chlorin, to investigate the role of metal in the center of the chlorophyllin chromophore. Adsorption of 37 different compounds, mostly mutagens, in 0.02 M Tris-HCl buffer at pH 8.0 to these chlorophyllin-Sepharose preparations was studied in a quantitative manner. The results showed that most of the compounds having three or more fused rings were strongly adsorbed with apparent dissociation constants of 10(-5)-10(-6) M, whereas those having two fused rings or one ring were only poorly adsorbed. Since the three Sepharose adsorbents gave similar adsorption profiles, it appeared that the central metal in the chlorophyllin molecule does not play a crucial role in the adsorption. We also measured the inhibitory effect of copper-chlorin against the mutagenicity of some of these compounds using the Salmonella assay. The results showed that those mutagens that were strongly adsorbable to copper-chlorin-Sepharose were subject to efficient inhibition by copper-chlorin, whereas many of those only poorly adsorbed were inhibited only weakly. We concluded that trapping by complex formation plays a role in the antimutagenic actions of chlorophyllin against many mutagens, particularly notable being the actions against ICR-170, quinacrine, aflatoxin B1, Trp-P-1 and Trp-P-2. An unusual behavior of Trp-P-2 in the adsorption process, i.e., a very tight complex formation at an extremely low Trp-P-2 concentration, was found; the implication of this phenomenon in relation to the real environmental setting is discussed.

Adsorption↗
PubMed1993

Porphyrins as potential inhibitors against exposure to carcinogens and mutagens.

Studies have shown that there are many substances that can interfere with the actions of carcinogens and mutagens. Porphyrins, which often are constituents of diet, are a class of such inhibitors. Hemin can inhibit selectively the activity of mutagens having polycyclic structures by forming complexes with them. These effects were found with the use of bacterial assays and also by in vitro chemical experiments. A survey of porphyrins for similar effects has been done in our laboratory and it was found that chlorophyll and chlorophyllin act like hemin. These green pigments are antimutagenic in Salmonella and in Drosophila. Work from other laboratories also has supported the antimutagenic character of chlorophyllin. The possibility of modifying human exposure to carcinogens by use of these porphyrins is discussed. A porphyrin-like molecule, copper phthalocyanine trisulfonate, has been shown to have strong affinity to polycyclic compounds. Blue cotton, a cotton preparation bearing this blue pigment as a covalently bound ligand, has been demonstrated to be an adsorbent useful for isolating heterocyclic amines from food and other materials.

Animals↗
PubMed1992

Suppression of genotoxicity of carcinogens by (-)-epigallocatechin gallate.

Epidemiological evidence shows that green tea may be a factor in lowering cancer risk. We have investigated the possibility that (-)-epigallocatechin gallate (EGCG), a major polyphenol in green tea, might be an antimutagenic substance. In the Ames Salmonella test, EGCG suppressed the direct-acting mutagenicity of 3-hydroxyamino-1-methyl-5H-pyrido-[4,3-b]indole (Trp-P-2(NHOH)) and 2-hydroxyamino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (Glu-P-1(NHOH)), the activated forms of food-derived carcinogens 3-amino-1-methyl-5H-pyrido[4,3-b]indole and 2-amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole. EGCG was also effective in reducing the mutagenicity of Trp-P-2(NHOH) in mouse FM3A cells in culture. Furthermore, EGCG demonstrated a suppressive effect in the in vivo Drosophila mutation assays, i.e., the wing spot test, and the DNA repair test, on several carcinogens. EGCG was also effective in inhibiting DNA single-strand breaks in vitro caused by Glu-P-1(NHOH). We conclude that the mechanism of inhibition may not have resulted from direct interaction between EGCG and the mutagens, but rather from indirect interception of mutagen action by EGCG.

Animals↗
PubMed1992

Modified metabolism of a carcinogen, 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2), by liver S9 from Schistosoma japonicum-infected mice.

Schistosoma japonicum infection has been associated with an increased incidence of liver and colorectal cancers in humans. To explore the mechanisms underlying this association, we investigated the carcinogen-metabolizing properties of liver S9 preparations from S. japonicum-infected mice and compared them with those of S9 from uninfected animals. When the carcinogen 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2) was incubated with these S9s and the products were analyzed by high-performance liquid chromatography, we observed that the S9 from infected mice had a lower ability to convert Trp-P-2 into 3-hydroxyamino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2(NHOH)), an activated form of promutagenic Trp-P-2, than the S9 from uninfected mice. We found that both of these S9 preparations have a high ability to reduce Trp-P-2(NHOH) into Trp-P-2; however, the infected-mouse S9 showed a significantly greater reducing power than the control S9. This difference appears to be responsible for the observed lower mutagen-activating potential of the infected mouse S9. These results suggest that hepatic enzyme activities of S. japonicum-infected mice are quantitatively different from those of normal mice.

Animals↗
PubMed1989

Formation of directly mutagenic alpha-hydroxy-N-nitrosopiperidine phosphate ester by near-ultraviolet irradiation of N-nitrosopiperidine in phosphate buffer.

Previously we found that direct-acting mutagens can be formed from N-nitrosodialkylamines on exposure to near-ultraviolet light in the presence of phosphates. We have now isolated the mutagenic photoproduct formed from N-nitrosopiperidine and inorganic phosphate and identified its structure as the phosphate ester of alpha-hydroxy-N-nitrosopiperidine. This reaction represents a new, non-enzymatic activation of promutagenic N-nitrosodialkylamines.

Buffers↗
PubMed1989

Role of hemin in the inhibition of mutagenic activity of 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2) and other aminoazaarenes.

The mechanism of inhibition by hemin of the mutagenic activities of food pyrolysate aminoazaarenes, particularly that of Trp-P-2 (3-amino-1-methyl-5H-pyrido[4,3-b]indole), was investigated. Hemin efficiently inhibited the metabolic activation by S9 of Trp-P-2, as demonstrated by high-performance liquid chromatographic analysis of the reaction mixtures in which Trp-P-2 had been treated with S9 in the presence or absence of hemin. N-Hydroxy-Trp-P-2, an activated form of Trp-P-2 having direct mutagenicity on Salmonella typhimurium TA98, undergoes spontaneous oxidative degradation in its aqueous solution, and the presence of hemin in the solution accelerated the degradation significantly. The presence of excess hemin with N-hydroxy-Trp-P-2 completely abolished the mutagenic activity of this mutagen towards Salmonella. A UV-visible spectroscopic study has suggested the formation of a complex between hemin and N-hydroxy-Trp-P-2/Trp-P-2. In support of this view, the fluorescence spectrum of a Trp-P-2 solution was quenched efficiently by the addition of hemin. These observations indicate that this complex formation plays a role in the observed multiple actions of hemin. Similar inhibitory actions of hemin on several other direct-acting aminoazaarene mutagens are also described, as well as the inhibition activities of protoporphyrin, chlorophyllin, biliverdin and bilirubin.

Biotransformation↗
PubMed1989

Evaluation of the mutagenicity and the tumor-promoting activity of parasite extracts: Schistosoma japonicum and Clonorchis sinensis.

In relation to the observed association of carcinogenesis with parasitic infections, the mutagenicity of extracts of Schistosoma japonicum and Clonorchis sinensis was examined. In the bacterial mutagenicity tests using the Ames Salmonella typhimurium strains TA98, TA100, TA97 and TA102, and Escherichia coli WP2 and WP2 uvrA pKM101 Schistosoma soluble egg antigen and a homogenate of adult Schistosoma worms showed no positive responses either in the presence or in the absence of S9 mix. Likewise, adult worm extracts of Clonorchis showed no mutagenicity. The Schistosoma soluble egg antigen showed a weak but significant activity for the induction of Epstein-Barr virus expression in viral genome-carrying human lymphoblastoid cells in culture. This phenomenon suggests that the soluble egg antigen possesses tumor-promoting activity.

Animals↗
PubMed1989

Reduced levels of mutagen processing potential in the Schistosoma japonicum-infected mouse liver.

Epidemiological studies have shown the presence of a positive correlation between the infection of Schistosoma japonicum and colorectal and/or liver cancers in the humans. To explore the mechanism underlying this correlation, we have investigated the mutagen-activating potentials of the liver homogenate fraction (S9) from Schistosoma japonicum infected mice and those from control mice, by use of the Ames test with 2-acetylaminofluorene, aflatoxin B1 and 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2) as test mutagens. Liver S9 prepared from the infected group at the 15th week after the infection showed a potential significantly lower than that from the control group. The hepatic cytochrome P-450 concentration in the infected mice was persistently low, about a half of that in the uninfected mice, during the period of 6-18 weeks after the infection. Thus, in mice bearing chronic schistosomiasis, mutagen-processing potentials are decreased.

2-Acetylaminofluorene↗
PubMed1989

Inhibitory effect of chlorophyll on the genotoxicity of 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2).

Genotoxicity of 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2) on Drosophila was suppressed by chlorophyll. Using the wing hair spot test, we found that the formation of mutant hairs in adult flies as a result of feeding them with Trp-P-2 in their larval stage was efficiently inhibited by coadministration of chlorophyll. The decrease in the spot frequencies was dependent on the dose of chlorophyll, and at the highest dose used, where the ratio in weight of Trp-P-2 to chlorophyll was 1:80, a complete prevention of the small single-spot formation was observed. A similar inhibitory effect was detected for chlorophyllin, the chromophore of chlorophyll. In the studies to investigate the mechanism of inhibition, we observed that the mutagenicity of 3-hydroxy-amino-1-methyl-5H-pyrido[4,3-b]indole [Trp-P-2(NHOH)], the metabolically activated form of Trp-P-2, in Salmonella typhimurium TA98 was suppressed effectively with chlorophyll and chlorophyllin. We also found that chlorophyll and chlorophyllin can produce complexes with Trp-P-2 and Trp-P-2(NHOH). A straightforward mechanism of these inhibitions is that Trp-P-2 [and Trp-P-2(NHOH)] becomes no longer available to organisms on forming the chlorophyll complex.

Animals↗