The in vivo micronucleus assay in mammalian bone marrow and peripheral blood. A report of the U.S. Environmental Protection Agency Gene-Tox Program

Mavournin, Kathleen H.; Blakey, David H.; Cimino, Michael C.; Salamone, Michael F.; Heddle, John A.

doi:10.1016/0165-1110(90)90030-f

Cited by 413 publications

(162 citation statements)

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“…The micronucleus assay was performed according to the US Environmental Protection Agency Gene-Tox Program [15] . Bone marrow from both femurs was collected after acute and subchronic treatments.…”

Section: Micronucleus Assaymentioning

confidence: 99%

“…Class 1 damage was the most frequent among the aripiprazole-damaged cells, which is considered a reparable minimal damage ( Figure 5). The micronucleus test was used to detect clastogenic/ aneugenic activities, which leads to an increasing frequency of micronuclei, and suggests mutagenic effects at the chromosomal level [15,26] . Aripiprazole has shown positive results in mutagenicity assays [27] .…”

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confidence: 99%

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Neurobehavioral and genotoxic parameters of antipsychotic agent aripiprazole in mice

et al. 2011

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Aim: Aripiprazole is an antipsychotic agent to treat schizophrenia, which acts through dopamine D 2 partial agonism, serotonin 5-HT 1A partial agonism and 5-HT 2A antagonism. This study was designed to evaluate the neurobehavioral effects and genotoxic/mutagenic activities of the agent, as well as its effects on lipoperoxidation. Methods: Open field and inhibitory avoidance tasks were used. Thirty min before performing the behavioral tasks, adult male CF-1 mice were administered aripiprazole (1, 3 or 10 mg/kg, ip) once for the acute treatment, or the same doses for 5 d for the subchronic treatment. Genotoxic effects were assessed using comet assay in the blood and brain tissues. Mutagenic effects were evaluated using bone marrow micronucleus test. Lipoperoxidation was assessed with thiobarbituric acid reactive substances (TBARS). Results: Acute and subchronic treatments significantly decreased the number of crossing and rearing in the open field task. Acute treatment significantly increased the step-down latency for both the short-and long-term memory in the inhibitory avoidance task. Subchronic treatments with aripiprazole (3 and 10 mg/kg) caused significant DNA strain-break damage in peripheral blood but not in the brain. Mutagenic effect was not detected in the acute and subchronic treatments. Nor TBARS levels in the liver were affected. Conclusion: Aripiprazole improved memory, but could impair motor activities in mice. The drug increased DNA damage in blood, but did not show mutagenic effects, suggesting that it might affect long-term genomic stability.Keywords: antipsychotic agent; aripiprazole; locomotion; memory; genotoxic/mutagenic activities; DNA damage; lipoperoxidation Acta Pharmacologica Sinica (2011Sinica ( ) 32: 1225Sinica ( -1232 doi: 10.1038/aps.2011 published online 15 Aug 2011 Original Article * To whom correspondence should be addressed. [8] .In the experimental context, Nagai et al [9] showed that aripiprazole that was administered as either a single dose or as consecutive doses (for 7 d) ameliorated phencyclidine-induced impairment of recognition memory in mice. However, another study showed that aripiprazole impaired the passiveavoidance response at doses near its anti-dopamine ED 50 (7.7 mg/kg, as defined by apomorphine stereotypy). At doses lower than those that affected the passive-avoidance response, aripiprazole was unable to reverse the MK-801-induced impairment in the same task [4] . Therefore, further investigations are necessary to elucidate the effect of aripiprazole on memory.The aim of the present study was to investigate the effects of aripiprazole on memory and on locomotor and exploratory activities with the inhibitory avoidance and open field tasks as behavioral models. Some drugs that affect memory can induce damage in biomolecules, such as lipids and DNA. Therefore, possible cytotoxic and genotoxic effects were evaluated by measuring lipid peroxidation in the liver and DNA strand breaks in both the peripheral blood and brain tissues after behavioral tasks. Mutagenic e...

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Section: Micronucleus Assaymentioning

confidence: 99%

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confidence: 99%

Neurobehavioral and genotoxic parameters of antipsychotic agent aripiprazole in mice

et al. 2011

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“…They provide a quantifiable measure of recent DNA injury that result from acentric fragments or whole chromosomes left behind the main nucleus at telophase. An increase in the frequency of micronucleated polychromatic erythrocytes (MNPCEs) in treated animals is an indication of induced chromosomal damage (Mavournin et al, 1990; OECD 474, 1997; Gonsebatt et al, 1997;Mahata et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

In Vivo Evaluation of Genotoxic Effect of Caralluma acutangula (Decne.) N.E.Br. extract on Mice Bone Marrow Cells

Al-Faifi¹

2017

IJASTR

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The current study was designed to evaluate the genotoxicity of Caralluma acutangula (Decne.) N.E.Br. extract on mice bone marrow cells in vivo. Two cytogenetics parameters were used, chromosomal aberrations assay and micronucleus test. Three different concentrations 125, 250, and 500 mg/kg body weight were chosen. Our results demonstrated that administration of C. acutangula extract did not significantly increase the number of structural chromosomal aberrations. No significant differences in the percentages of mitotic indices were observed at the three different concentrations of C. acutangula extract. In micronucleus test, treatment with C. acutangula extract caused no significant increase in the number of polychromatic erythrocytes with micronuclei or in the mean percentage of polychromatic. In conclusion, C. acutangula extract showed no significant genotoxic effect on mice bone marrow cells in vivo.

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“…The micronucleus (MN) assay in rodents is the bestdocumented in vivo test on clastogenic effects (chromosome aberrations), in relation to the number of tested chemicals (Mavournin et al, 1990;Morita et al, 1997) and chromosome aberration test is an important cytogenetic endpoint that is routinely used to evaluate genotoxicity (Preston et al, 1987;Krishna et al, 1991). In the present study, it was demonstrated that three high doses of A. populnea chloroform fraction from crude barkwood extract showed no increase in the mean number of micronucleated erythrocytes in the peripheral blood of mice, and the bone marrow of rats, and no chromosomal aberrations in the bone marrow cells of Wistar rats.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the genotoxic potential of Austroplenckia populnea (Reiss) Lundell chloroform fraction from barkwood extract in rodent cells in vivo

et al. 2009

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The genotoxic effect of the Austroplenckia populnea chloroform fraction from barkwood extract was tested in vivo on peripheral blood cells of Swiss mice with the comet assay (SCGE), and the clastogenic effect was investigated on peripheral blood cells of Swiss mice and bone marrow cells of Wistar rats, with the micronucleus and chromosome aberrations tests. The animals were treated by gavage with 3 concentrations of the extract: 300, 600 and 900 mg.kg -1. Peripheral blood cells of Swiss mice were collected 4 and 24 hours after the treatment to the SCGE assay and 48 and 72 hours to the micronucleus test. Bone marrow cells of Wistar rats were collected 24 hours after the treatment to the micronucleus and chromosome aberration tests. The results showed that the A. populnea chloroform fraction induced an increase in the average number of DNA damage in peripheral blood cells at the three concentrations tested, but this increase was not statistically significant. In the micronucleus and chromosome aberrations test, no significant increase was observed in the mean number of micronucleated polychromatic erythrocytes (MNPCE) of Swiss mice or MNPCE or chromosome aberrations for the rat bone marrow cells, for any of the tested doses. Our findings enable us to conclude that by the comet assay, A. populnea chloroform fraction from barkwood extract showed no genotoxic effects, and by the micronucleus and chromosome aberration tests, the extract fraction showed no clastogenic/aneugenic effects on the rodent cells tested.Keywords: Austroplenckia populnea, celastraceae, micronucleus test, single cell gel electhrophoresis, chromosome aberrations. Avaliação do potencial genotóxico da fração clorofórmica de cascas do caule de Austroplenckia populnea em células de roedores in vivo ResumoO possível efeito genotóxico da fração clorofórmica de cascas de caule de Austroplenckia populnea foi testado in vivo em células do sangue periférico de camundongos Suíços pelo ensaio cometa, e o seu possível efeito clastogênico foi investigado em células de sangue periférico de camundongos Suíços e células da medula óssea de ratos Wistar, respectivamente pelos testes do micronúcleo e de aberrações cromossômicas. Os animais foram tratados por via oral com três concentrações do extrato: 300, 600 e 900 mg.kg -1 de peso corpóreo. Células do sangue periférico dos camundongos foram coletadas 4 e 24 horas após o tratamento para a realização do ensaio cometa, e 48 e 72 horas para o teste do micronúcleo. Células da medula óssea dos ratos Wistar foram coletadas 24 horas após o tratamento para os testes do micronúcleo e de aberrações cromossômicas. Os resultados mostraram que a fração clorofórmica do extrato de A. populnea induziu um pequeno aumento no número médio de danos ao DNA nas células sanguíneas nas três concentrações testadas, mas tal aumento não foi estatisticamente significativo. Nos testes do micronúcleo e de aberrações cromossômicas não houve um aumento significativo no número médio de eritrócitos policromáticos micronucleados (EPM) dos ca...

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The in vivo micronucleus assay in mammalian bone marrow and peripheral blood. A report of the U.S. Environmental Protection Agency Gene-Tox Program

Cited by 413 publications

References 192 publications

Neurobehavioral and genotoxic parameters of antipsychotic agent aripiprazole in mice

Neurobehavioral and genotoxic parameters of antipsychotic agent aripiprazole in mice

In Vivo Evaluation of Genotoxic Effect of Caralluma acutangula (Decne.) N.E.Br. extract on Mice Bone Marrow Cells

Evaluation of the genotoxic potential of Austroplenckia populnea (Reiss) Lundell chloroform fraction from barkwood extract in rodent cells in vivo

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