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H Tokiwa

Publications and source records attributed to H Tokiwa.

At least 55 records · Page 3Linked to original sources
PubMed1987

The nature of the mutagenicity and carcinogenicity of nitrated, aromatic compounds in the environment.

Gaseous substances such as nitrogen dioxide (NO2) and sulfur dioxide (SO2) stimulate the process of nitration of polycyclic aromatic hydrocarbons, and the transformation products display a broad spectrum of mutagenicity, genotoxicity, and carcinogenicity. Bacterial mutation by nitroarenes is specific. Tetracyclic nitroarenes are thought to be the most mutagenic compounds in the Salmonella test system, and some are carcinogenic in rats and mice. Furthermore, it was found that the mutational nitroarenes produced mostly DNA damage, which is subject to recombination repair in the rec assay system using Bacillus subtilis. Nitroarenes in the environment seem to be ubiquitous; the majority of the compounds are emitted directly from diesel emissions, kerosene heaters, and gas and liquefied-gas burners or heaters. In nitroarenes induced during incomplete combustion, nitropyrene and nitrofluoranthene derivatives are the most important mutagens/carcinogens for determining the chronic toxicity of nitroarenes overall.

Animals↗
PubMed1987

Tumorigenicity test of 1,3- and 1,8-dinitropyrene in BALB/c mice.

1,3-Dinitropyrene (DNP) and 1,8-DNP (CAS: 42397-65-9) are very potent mutagens and induce a frameshift-type mutation in the Salmonella test system. Each compound was tested for tumorigenicity in BALB/c mice by sc inoculation of 0.05 mg of the compound once a week for 20 weeks. Tumors developed at the site of injection of 1,8-DNP in 6 of 15 mice up to 60 weeks after the first injection. The incidence of tumors was statistically significant at a P-value of less than .05 but not of less than .01. Therefore, the carcinogenicity of 1,8-DNP in BALB/c mice was concluded to be weaker than that of benzo[a]pyrene [(BP) CAS: 50-32-8], which induced a 100% tumor incidence when it was injected at the same dose as that of 1,8-DNP. No tumors occurred at the injection site in mice given 1,3-DNP. Most of the tumors induced by 1,8-DNP and BP showed histologic features characteristic of malignant fibrous histiocytoma.

Animals↗
PubMed1986

Adjuvant activity of diesel-exhaust particulates for the production of IgE antibody in mice.

The prevalence rate of allergic rhinitis caused by pollen has strikingly increased in Japan in the last three decades. The number of diesel cars in use has also rapidly increased in the country. This fact urged us to study the effects of particulates emitted from diesel cars on the production of IgE antibody. The primary IgE antibody responses in mice immunized with intraperitoneal injection of ovalbumin (OA) mixed with diesel-exhaust particulates (DEP) were higher than those in the animals immunized with OA alone. This effect of DEP on the production of IgE antibody in mice was also demonstrated when mice were immunized with repeated injections of dinitrophenylated-OA. In addition, persistent IgE-antibody response to major allergen of Japanese cedar pollen (JCPA), a most common pollen causing allergic rhinitis in Japan, was observed in mice immunized with JCPA mixed with DEP but not in the animals immunized with JCPA alone. The results do indicate that the adjuvant activity of DEP can not be excluded as a possible cause of the associated change in the number of diesel cars and allergic rhinitis caused by pollen in Japan.

Adjuvants, Immunologic↗
PubMed1986

Mutagenicity and carcinogenicity of nitroarenes and their sources in the environment.

Nitroarenes are postulated to play a principal part among mutagens/carcinogens which are induced in the combustion process and, in addition, are widely distributed in the environment. This review deals with the following points concerning nitroarene toxicity. Data on the mutagenicity of nitroarenes obtained by short-term bioassays are expected to provide us with sufficient information for us to determine their genotoxicity and carcinogenicity. Therefore, mutagenicity detected with Salmonella, Escherichia, and yeast test systems is discussed. Genotoxicity in mammalian cells is also important for determining the mutagenic properties of nitroarenes. In this article, mutagenicity in Chinese hamster ovary cells, sister chromatid exchanges, and cell transformation is summarized. The metabolism of nitroarenes in vivo and in vitro is of importance for determining their behavior and active forms. Therefore, current studies regarding metabolism of nitroarenes are described. Carcinogenicity of nitroarenes for animals has been reported by many workers. In this review, the incidence and histological features of tumors induced by nitroarenes are described. Furthermore, the possible association between human lung cancer and nitroarenes is discussed. Sources of nitroarenes in the environment are given. The results of various chemical tests for identifying nitroarenes are summarized, and speculation on the risk of nitroarenes for humans is presented.

Animals↗
PubMed1986

Dinitro derivatives of pyrene and fluoranthene in diesel emission particulates and their tumorigenicity in mice and rats.

A number of mutagens/carcinogens in diesel emission particulates are produced and distributed into the atmosphere. On the basis of the results of chemical analysis, it was found that most of the mutagenicity in diesel particulate extracts is due to super-mutagens such as 1,3-, 1,6- and 1,8-DNP, and 3,7- and 3,9-DNF. 3,7- and 3,9-DNF are new mutagens which were isolated in this study and they induced a frameshift type mutation in the Salmonella microsome test. Each derivative of DNP and DNF was detected at a concentration of 0.01 to 0.03 ppm in the particulates while the diesel engine was used under the condition of idling. 1,6- and 1,8-DNP were tumorigenic at the injection site in BALB/c male mice when a total of 2 and 1 mg, respectively, of the compounds was given subcutaneously. The incidences for tumors by 60 weeks were at a ratio of 50 and 30%, respectively, for 1,6- and 1,8-DNP-treated mice. 4-NQO and BaP, as positive control, induced tumors at the injection site in BALB/c mice when a total of 2 and 1 mg, respectively, of the compound was given. The incidences of tumors were observed at a high ratio of 90 and 93.4%, respectively, for 4-NQO- and BaP-treated mice. Histologically the tumors were diagnosed as malignant fibrous histiocytomas in all the tumors which developed. No tumors occurred at the injection site in mice given injections of 1,3-DNP. Tumorigenicity tests of 3,7- and 3,9-DNF are now being attempted using F344/DuCrj male rats. This animal experiment is now in progress. In the 3,9-DNF-treated rats (a total of 1 mg per rat), subcutaneous tumors developed in 8 of 11 rats up to 150 days after injection, and a part of a tumor resected from a rat showed the typical features of rhabdomyosarcoma.

Animals↗
PubMed1985

Mutagenic/carcinogenic agents in indoor pollutants; the dinitropyrenes generated by kerosene heaters and fuel gas and liquefied petroleum gas burners.

Incomplete combustion of kerosene heater, and fuel gas and liquefied petroleum gas-burner emissions produces indoor pollutants that may be carcinogenic. The incomplete-combustion products from each type of appliance were therefore collected by adsorption on about 3 g of XAD-2 resin, and were extracted with benzene-methanol as a solvent for determination and identification of mutagens in the Salmonella-microsome test system. Benzene-methanol extracts of the particulates generated by a heater and two burners showed extreme mutagenicity for strains TA97 and TA98 without S9 mix. Based on the results of analysis, a combination of high performance liquid chromatography (h.p.l.c.) and gas chromatography (GC), about 40-80% of the direct-acting mutagenicity in each crude extract showed the same h.p.l.c. and GC retention times as dinitropyrenes (1,3-, 1,6- and 1,8-isomers), and 1-nitropyrene. Moreover, other nitroarenes, 2-nitrofluorene, 1,5- and 1,8-dinitronaphthalene, and 4,4'-dinitrobiphenyl, were detectable in almost all samples, but their contribution to the mutagenicity of each extract was very low. Kerosene heaters were found to generate small amounts (0.2 ng/h) of dinitropyrenes, which are potential mutagens/carcinogens, only after 1 h of operation.

Air Pollutants↗
PubMed1984

1,6-Dinitropyrene: mutagenicity in Salmonella and carcinogenicity in BALB/c mice.

In tests on the carcinogenicity of 1,6-dinitropyrene [(1,6-DNP) CAS: 42397-64-8] and 1-nitropyrene [(1-NP) CAS: 5522-43-0], 0.1 mg of each compound was inoculated sc into BALB/c mice once a week for 20 weeks. In the group given injections of 1,6-DNP the first tumor appeared on day 112, and 10 of the 20 mice developed tumors at the injection site by 45 weeks after the first injection. However, no tumors were induced in any of the mice that received injections of 1-NP. All of the induced tumors were transplantable for more than five generations in male BALB/c mice. Most of the tumors showed the characteristic histologic features of malignant fibrous histiocytoma.

Animals↗
PubMed1983

Some findings on mutagenicity in airborne particulate pollutants.

Mutagenic activity in particulate airborne pollutants in several samples collected in a wide variety of industrial, residential, and small-scale factory districts over the past seven years was detected by the Ames test. The particulate air samples that were not contaminated with several chemicals such as NO (less than 0.001 ppm), NO2 (less than 0.001 ppm), and SO2 (less than 0.001 ppm) showed only low mutagenic activity (1 revertant/m3) when they were tested with Salmonella typhimurium strain TA98 in the presence of S9 mix. However, most of the samples polluted by particulate matters showed high mutagenicity, with responses varying from 2.4 to 445 revertants per m3: 67 samples from an industrial area induced an average of 44 revertants per m3; 60 from a residential area, 16.2; and 10 from a small-scale factory area, 72.1. For assessing the mutagenic potential of the pollution in the atmosphere, the frequency of mutation determined with strain TA98 in the presence of S9 mix was used to divide the samples tentatively into five groups (A-E) on the basis of the normal logarithmic distribution curve of 137 samples. Air samples belonging to group A gave less than 2.3 revertants per m3 of air (1.12 +/- 0.12, no pollution); those of group B gave a range of 2.4 to 8.6 (5.93 +/- 1.91, slight pollution); those of group C gave a range of 8.7 to 30.2 (16.0 +/- 5.36, moderate pollution); those of group D gave a range of 30.3 to 115 (56.7 +/- 20.1, considerable pollution); and those of group E gave more than 116 (234 +/- 119, heavy pollution). Of the 137 samples tested, 6 samples (4.4%) were assigned to group A, 38 (27.7%) to group B, 52 (38.0%) to group C, 34 (24.8%) to group D, and 7 (5.1%) to group E. Furthermore, the samples in an industrial area were classified in the order of group C (35.8%), group B (26.9%), group D (22.4%), group E (8.96%), and group A (5.97%), and those in a residential area in the order of group C (46.7%), group B (33.3%), group D (18.3%), and group A (1.67%).

Air Pollutants↗
PubMed1983

Identification of dinitropyrenes in diesel-exhaust particles. Their probable presence as the major mutagens.

The direct-acting mutagens in diesel particulate extracts were identified. It is concluded that the major mutagens are in all probability 1,6- and 1,8-dinitropyrene (DNP). 1-Nitropyrene (NP) and 3-nitrofluoranthene (NF) were also present. The DNP isomers contributed 43% of the total mutagenic activity of the crude extracts, whereas 1-NP (or 3-NF) was responsible for less than 10% of the activity. The quantities of 1,6- and 1,8-DNP were 1.2 and 3.4 ppm of the crude extracts, respectively, and the induction of both DNPs in the diesel particulate matter corresponded to about 1.7-4.8% by weight of the 1-NP content (70.5 ppm in the crude extracts).

Chromatography, High Pressure Liquid↗
PubMed1983

Demonstration of a powerful mutagenic dinitropyrene in airborne particulate matter.

Of the many nitroarenes, dinitropyrenes (DNPs) have the potential to revert Salmonella typhimurium his- mutants. This study was conducted to investigate the potential mutagens present in airborne particulate matter collected in Santiago, Chile. 5 organic substances extracted with dichloromethane showed mutagenic rates of from 38.9 to 287 revertants per m3 of air for S. typhimurium his- strain TA98 without S9 mix. 4 of the samples had greatly reduced mutagenicity for strain TA98/1,8DNP6 but not for strain TA98NR. The 1-nitropyrene (1-NP) content accounted for 0.06-0.15 microgram per g of particulate, as determined by high-performance liquid chromatography (HPLC), but the contribution of the compound to mutagenicity was less than 1% of the total activity. On the other hand, by using two columns in the HPLC, DNPs of 1,6- and 1,8-isomers were detected in the samples pooled after the determination of 1-NP, and the amount of the derivatives was about 0.2 microgram per g of particulate matter.

Air Pollutants↗
PubMed1983

Detection and characterization of polymers in cephalothin by passive cutaneous anaphylaxis in mice.

Immunization of BALB/c mice by repeated injections of cephalothin (CET) - Ascaris suum extract conjugate resulted in formation of IgE antibodies, which were able to sensitize syngeneic animals for passive cutaneous anaphylaxis (PCA). By means of high-pressure liquid chromatography, a fraction with extremely high PCA-eliciting activity, but without appreciable antimicrobial activity, was isolated from the CET preparation. Physicochemical analyses of the fraction identified the major component of polymer impurities as being a proteinaceous complex with a molecular weight of 6,580. Very little cross-reactivity of CET and potassium benzyl penicillin (PcG) was noted when these antibiotics were used as the challenge antigens for PCA induced by corresponding murine antisera. The results of the inhibition studies indicated, however, that at least two antigens were involved in the PCA induced by anti-CET antibodies, one strictly specific for CET and another shared by PcG. Evidence was also presented that the nucleus structure and acyl side-chain structure of CET play the major role in the PCA elicited by the challenge with CET and its polymer, respectively.

Animals↗
PubMed1982

Carcinogenicity in rats of the mutagenic compounds 1-nitropyrene and 3-nitrofluoranthene.

1-Nitropyrene and 3-nitrofluoranthene are present in diesel exhaust, in pollutants in air, and were also present in certain xerographic toners and copies. Their carcinogenicities were studied in male F344/DuCrj rats by subcutaneous injection. Sarcomas, mainly malignant fibrous histiocytomas at the site of injection were induced in 8 to 17 (47%) rats by 1-nitropyrene and in 4 of 10 (40%) rats by 3-nitrofluoranthene. Some tumors were serially transplantable in the same strain of rats.

Air Pollutants↗
PubMed1982

Antigenicity of beta-lactam antibiotic preparations: production of IgE antibodies to beta-lactam antibiotic and their cross-reaction within the antibiotic group.

BALB/C mice were immunized with conjugate of benzylpenicillin or ampicillin with Ascaris suum extract. The mice developed IgE antibodies to penicillin, which were found to react with commercially available penicillin preparations in the PCA system. Elimination of polymerized penicillin by Sephadex chromatography from tested preparations could not diminish their activities to elicit PCA. High pressure liquid chromatographic (HPLC) separation of PcG preparation yielded fractions unable to elicit PCA. On the other hand, all fractions from ABPC retained the activity even after the HPLC purification. A comparative estimation of cross-reactivity of IgE and IgE antipenicillin antibodies showed that IgE antibodies cross-reacted with a variety of beta-lactam antibiotics in a high degree.

Ampicillin↗
PubMed1981

Mutagenicity of nitro derivatives induced by exposure of aromatic compounds to nitrogen dioxide.

Mutagenic nitro derivatives were readily induced when 6 kinds of chemicals were exposed to 10 ppm of nitrogen dioxide (NO2). Single nitro derivatives were formed from pyrene, phenanthrene, fluorene or chrysene. Carbazole and fluoranthene each produced 2 derivatives substituted with nitro groups at different positions. The formation of nitro derivatives was enhanced by exposure of pyrene to NO2 containing nitric acid (HNO3, less than 100-fold enhancement) or sulphur dioxide (SO2, less than 15-fold enhancement). After 24 h of exposure the yields of the nitro derivative were 0.02% with 1 ppm of NO2 in air and 2.85% with NO2 (1 ppm) containing traces of HNO3. The nitro derivatives from all but phenanthrene and carbazole were chemically identified by means of gas chromatography (GC) and mass spectrometry (MS), and the mutagenicity of the 4 kinds of authentic nitro derivatives was tested by using Salmonella strains TA98 and TA1538 with or without the S9 fraction from rat liver treated with Aroclor 1254. The nitro derivative induced from pyrene was determined to be 1-nitropyrene; that of chrysene was 6-nitrochrysene; that of fluorene was 2-nitrofluorene; and those of fluoranthene were 3-nitrofluoranthene, and 8-nitrofluoranthene. Tested with strain TA98 in the absence of the S9 fraction, the first 4 of these derivatives yielded, respectively, 3050, 269, 433 and 13 400 revertants per nmole. Thus, each nitro derivative formed was potentially a direct-acting frameshift-type mutagen. Each compound exposed to NO2 showed a decreased mutagenic activity when tested in the presence of S9 mix. A possible explanation comes from experiments in which 1-nitropyrene was incubated with the S9 mix at 37 degree C for 10 min, and 1-aminopyrene was formed. The mutagenic activity of 1-aminopyrene was appreciable, but only about one-tenth of that of 1-nitropyrene in the Ames test.

Heterocyclic Compounds↗
PubMed1981

FK phage for differentiating the classical and El T or groups of Vibrio cholerae.

A new vibrio-infecting phage (FK phage) isolated from sewage lysed all strains of Vibrio cholerae biovar cholerae, whereas all strains of V. cholerae biovar El Tor were resistant to it. FK phage was entirely different from Mukerjee group IV phage in morphology and antigenicity. In addition to group IV phage, the use of FK phage will be useful in the examination and typing of V. cholerae.

Antigens, Viral↗
PubMed1980

Detection of mutagenic activity in automobile exhaust.

Using the Ames Salmonella-microsome system, we detected mutagenic activity in the exhaust from two kinds of 4-cycle gasoline engines of unregulated and regulated cars, and from diesel engines, as well as in the particulates from air collected in tunnels. The mutagenicity of particulates from a car equipped with a catalyst (regulated car), as compared with that from an unregulated car, was reduced very much (down to 500 from 4500 revertants/plate/m3 in tester strain TA98). However, the mutagenicity of the ether-soluble acid and neutral fractions from the condensed water of emissions from a regulated car was still high (down to 2880 from 10 900 revertants/plate/m3 in tester strain TA100). The mutagenic activity of emission exhaust from old diesel car engines was very high; the particulates showed 9140 and 19 600 revertants/plate/m3 from strain TA98 incubated with an activating rat-liver S9 fraction. A small diesel engine of the type used for the generation of electric power or in farm machinery also produced exhaust with highly mutagenic particulates. The mutagenic activity of a methanol extract of particulate air pollutants collected in a highway tunnel showed 39 revertants/plate/m3 toward strain TA98 and 87 toward strain TA100. The ether-soluble neutral fraction yielded 86 revertants/plate/m3 from strain TA98 and 100 from strain TA100. This fraction also contained carcinogenic compounds, including benzo[a]pyrene, benzo[e]pyrene, benz[a]anthracene, benzo[ghi]perylene and chrysene. Very high mutagenic activity was detected, especially in the particulate air pollutants collected at night, in another tunnel on a superhighway: 60-88 revertants/plate/m3 from strain TA100 for the sample collected by day, but 121-238, by night. Night traffic includes many more diesel-powered vehicles compared with gasoline-powered automobiles.

Air Pollutants↗