Modifying role of Phyllanthus emblica and ascorbic acid against nickel clastogenicity in mice.
TL;DR: Aqueous extract of edible dried fruits of Phyllanthus emblica was fed to Mus musculus for seven consecutive days prior to treatment with different doses of nickel chloride, finding the greater efficacy of the fruit extract could be due to the interaction of its various natural components rather than to any single constituent.
About: This article is published in Cancer Letters.The article was published on 1991-07-26. It has received 59 citations till now. The article focuses on the topics: Dried fruit & Ascorbic acid.
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TL;DR: Seven plants contain antioxidant principles, that can explain and justify their use in traditional medicine in the past as well as the present, and are viewed for their historical, etymological, morphological, phytochemical and pharmacological aspects.
801 citations
01 Aug 2005
363 citations
Cites background from "Modifying role of Phyllanthus embli..."
...The nickel-induced DNA damage has resulted in the formation of chromosomal aberrations (Conway and Costa 1989; Dhir et al. 1991; Larramendy et al. 1981; Lechner et al. 1984; Sen and Costa 1986b; Sen et al. 1987; Waksvcik and Boysen 1982) that could result in deletion of senescence or tumor suppressor genes....
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...Chromosome gaps or chromosome aberrations have been reported in lymphocytes from nickel refinery workers (Waksvik and Boysen 1982), mouse bone marrow cells following intraperitoneal injection (Dhir et al. 1991), and in in vitro assays using hamster cells (Conway and Costa 1989; Larramendy et al....
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Journal Article•
TL;DR: Structural-activity relationship analysis suggested that the micronucleus assay is more sensitive to the genetic toxicity of some classes of chemicals than to those carcinogens with stronger evidence human carcinogenicity.
268 citations
TL;DR: In the 6th MMS/CSGMT collaborative study as mentioned in this paper, IARC groups 1 (human carcinogen), 2A (probable human carcinogen) and 2B (possible human carcinogens) were selected from 100 commercially available chemicals and chemical groups on which there was little or no micronucleus assay data.
Abstract: To assess the correlation between micronucleus induction and human carcinogenicity, the rodent micronucleus assay was performed on known and potential human carcinogens in the 6th MMS/CSGMT collaborative study Approximately 100 commercially available chemicals and chemical groups on which there was little or no micronucleus assay data were selected from IARC (International Agency for Research on Cancer) Groups 1 (human carcinogen), 2A (probable human carcinogen) and 2B (possible human carcinogen) As minimum requirements for the collaborative study, 5 male mice were treated by intraperitoneal injection or oral gavage once or twice with each chemical at three dose levels, and bone marrow and/or peripheral blood was analyzed Five positives and 2 inconclusives out of 13 Group 1 chemicals, 7 positives and 5 inconclusives of 23 Group 2A chemicals, and 26 positives and 6 inconclusives of 67 Group 2B chemicals were found Such low positive rates were not surprising because of a test chemical selection bias, and we excluded well-known micronucleus inducers The overall evaluation of the rodent micronucleus assay was based on the present data combined with published data on the IARC carcinogens After merging, the positive rates for Groups 1, 2A and 2B were 686, 545 and 456%, respectively Structure-activity relationship analysis suggested that the micronucleus assay is more sensitive to the genetic toxicity of some classes of chemicals Those to which it is sensitive consist of (1) aziridines and bis(2-chloroethyl) compounds; (2) alkyl sulfonate and sulfates; (3) acyl-type N-nitroso compounds; (4) hydrazines; (5) aminobiphenyl and benzidine derivatives; and (6) azo compounds Those to which it is less sensitive consist of (1) dialkyl type N-nitroso compounds; (2) silica and metals and their compounds; (3) aromatic amines without other functional groups; (4) halogenated compounds; and (5) steroids and other hormones After incorporation of structure-activity relationship information, the positive rates of the rodent micronucleus assay became 905, 652 and 600% for IARC Groups 1, 2A and 2B, respectively Noteworthy was the tendency of the test to be more sensitive to those carcinogens with stronger evidence human carcinogenicity
251 citations
TL;DR: There is no convincing evidence that any genotoxic rodent carcinogens or in vivo genotoxins would remain undetected in an in vitro test battery consisting of Ames+MNvit.
Abstract: In vitro genotoxicity testing needs to include tests in both bacterial and mammalian cells, and be able to detect gene mutations, chromosomal damage and aneuploidy. This may be achieved by a combination of the Ames test (detects gene mutations) and the in vitro micronucleus test (MNvit), since the latter detects both chromosomal aberrations and aneuploidy. In this paper we therefore present an analysis of an existing database of rodent carcinogens and a new database of in vivo genotoxins in terms of the in vitro genotoxicity tests needed to detect their in vivo activity. Published in vitro data from at least one test system (most were from the Ames test) were available for 557 carcinogens and 405 in vivo genotoxins. Because there are fewer publications on the MNvit than for other mammalian cell tests, and because the concordance between the MNvit and the in vitro chromosomal aberration (CAvit) test is so high for clastogenic activity, positive results in the CAvit test were taken as indicative of a positive result in the MNvit where there were no, or only inadequate data for the latter. Also, because Hprt and Tk loci both detect gene-mutation activity, a positive Hprt test was taken as indicative of a mouse-lymphoma Tk assay (MLA)-positive, where there were no data for the latter. Almost all of the 962 rodent carcinogens and in vivo genotoxins were detected by an in vitro battery comprising Ames+MNvit. An additional 11 carcinogens and six in vivo genotoxins would apparently be detected by the MLA, but many of these had not been tested in the MNvit or CAvit tests. Only four chemicals emerge as potentially being more readily detected in MLA than in Ames+MNvit--benzyl acetate, toluene, morphine and thiabendazole--and none of these are convincing cases to argue for the inclusion of the MLA in addition to Ames+MNvit. Thus, there is no convincing evidence that any genotoxic rodent carcinogens or in vivo genotoxins would remain undetected in an in vitro test battery consisting of Ames+MNvit.
203 citations
Additional excerpts
...Nickel chloride Nickel chloride hexhydrate 7718-54-9 7791-20-0 E + [985]; − TC [370,474,986, 987]; I [988]; − [989] + [990, 991]; gpt [992]; HPRT [388,993] + [392,785] + + [994–999]; Weak + [1000] E + [1001,1002]; − [120,1003] + [1002] + [1004,1005]...
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...[1002] H....
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References
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TL;DR: The data reported here indicate that chlorophyllin is potentially useful as an antimutagenic agent.
Abstract: Chlorophyllin, the sodium and copper salt of chlorophyll, was tested for its ability to inhibit the mutagenic activity of a variety of complex mixtures--extracts of fried beef, fried shredded pork, red grape juice, red wine, cigarette smoke, tobacco snuff, chewing tobacco, airborne particles, coal dust and diesel emission particles--in strain TA98 of Salmonella typhimurium. Chlorophyllin was highly effective against the mutagenicity (90-100% inhibition) of 8 of these 10 mixtures. The mutagenicity of the other 2 mixtures was inhibited 75-80% at the highest concentration of chlorophyllin studied. Control and reconstruction experiments showed that chlorophyllin was not toxic to Salmonella at the concentrations used. The antimutagenic activity of chlorophyllin was heat-stable. The mechanism of the antimutagenicity of chlorophyllin in these experiments is not known; however, chlorophyllin is an antioxidant. Scavenging of radicals and/or interaction with the active group of mutagenic compounds may be responsible for its antimutagenic activity. The data reported here indicate that chlorophyllin is potentially useful as an antimutagenic agent.
217 citations
153 citations
TL;DR: Thirty-two workers in an electroplating plant accidently drank water contaminated with nickel sulfate and chloride and promptly developed symptoms that typically lasted a few hours but persisted 1-2 days in 7 cases, resulting in a mean elimination half-time for serum Ni of 27 hours (SD +/- 7 hour), which was significantly shorter than the mean T1/2 of 60 hours in 11 subjects who did not receive intravenous fluids.
Abstract: Thirty-two workers in an electroplating plant accidently drank water contaminated with nickel sulfate and chloride (1.63 g Ni/liter). Twenty workers promptly developed symptoms (e.g., nausea, vomiting, abdominal discomfort, diarrhea, giddiness, lassitude, headache, cough, shortness of breath) that typically lasted a few hours but persisted 1-2 days in 7 cases. The Ni doses in workers with symptoms were estimated to range from 0.5 to 2.5 g. In 15 exposed workers who were tested on day 1 postexposure, serum Ni concentrations ranged from 13 to 1,340 micrograms/liter and urine Ni concentrations ranged from 0.15 to 12 mg/g creatinine. Ten subjects (with initial urine Ni concentrations greater than 0.8 mg/g creatinine) were hospitalized and treated for 3 days with intravenous fluids to induce diuresis, resulting in a mean elimination half-time (T1/2) for serum Ni of 27 hours (SD +/- 7 hour), which was significantly shorter (p less than .001) than the mean T1/2 of 60 hours (SD +/- 11 hours) in 11 subjects who did not receive intravenous fluids. Laboratory tests showed transiently elevated levels of blood reticulocytes (N = 7), urine albumin (N = 3), and serum bilirubin (N = 2). All subjects recovered rapidly, without evident sequellae, and returned to work by the eighth day after exposure.
138 citations
TL;DR: It is suggested that a substantial proportion of the resources currently available for conducting rodent carcinogenicity bioassays should be employed in the short-term evaluation in vivo of some of the many hundreds of chemicals recently defined as genotoxic in vitro, rather than in the protracted evaluation of a few chemicals.
Abstract: Some of the probable reasons underlying the observation that not all chemicals shown to be genotoxic in vitro are capable of eliciting tumours in rodents or humans are discussed using appropriate examples. It is suggested that a substantial proportion of the resources currently available for conducting rodent carcinogenicity bioassays should be employed in the short-term evaluation in vivo of some of the many hundreds of chemicals recently defined as genotoxic in vitro, rather than in the protracted evaluation of a few chemicals, often of unknown activity in vitro, for carcinogenicity. A decision tree approach to the evaluation of chemicals for human mutagenic/carcinogenic potential is presented which is at variance with the construction and philosophy of many of the current legislative guidelines. The immediate need for the adoption of one of the available short-term in vivo liver assays, and/or the development of a short-term in vivo rodent assay capable of concomitantly monitoring different genetic end-points in a range of organs or tissues is emphasized.
94 citations
TL;DR: The results demonstrate that exposure to MIC by inhalation results in bone marrow damage, indicating the systemic genotoxic/cytotoxic activity of MIC and/or reactive metabolites.
Abstract: The ability of inhaled methyl isocyanate (MIC) to induce genotoxic and cytotoxic damage in vivo was evaluated by assessing the induction of chromosomal aberrations (CAs) and sister chromatid exchanges (SCEs) in bone marrow metaphase cells, the induction of micronuclei in polychromatic erythrocytes (MN-PCEs), and the inhibition of bone marrow cellular proliferation and erythropoiesis. B6C3F1 mice were exposed to MIC by two exposure regiments: in two experiments, male mice only were exposed to 3, 10, and 30 ppm for 2 hr; in four experiments, male and female mice were exposed to 1 and 3 ppm (in one experiment, to 6 ppm, also), 6 hr per day for 4 consecutive days. The various cytogenetic endpoints were analyzed in bone marrow and peripheral blood (4-day exposure regimen only) samples taken from bromodeoxyuridine tablet-implanted animals killed 11 to 22 hr after cessation of the exposure to MIC. Exposure to MIC for 2 hr induced a significant delay in cellular proliferation but did not induce a significant increase in CAs, SCEs (evaluated at 3 and 10 ppm, only) or in bone marrow MN-PCEs. Also, this exposure regimen did not inhibit the rate of erythropoiesis. Following exposure to MIC for 4 days, a weak but significant increase in CAs and SCEs was observed in male (in one experiment) and in female (in two experiments) mice. The induction was especially apparent in the single experiment in which mice were exposed to 6 ppm MIC. At this concentration, a significant increase in MN-PCEs in peripheral blood was observed in male but not female mice. Delay in bone marrow cell proliferation was observed in male mice beginning at 3 ppm and in female mice at 6 ppm. The 4-day exposure regimen resulted also in a depressed rate of erythropoiesis, with male mice appearing to exhibit greater depression than female mice. The results demonstrate that exposure to MIC by inhalation results in bone marrow damage, indicating the systemic genotoxic/cytotoxic activity of MIC and/or reactive metabolites.
88 citations