Towards an improved micronucleus test Studies on 3 model agents, mitomycin C, cyclophosphamide and dimethylbenzanthracene

Salamone, Michael F.; Heddle, John A.; Stuart, Earl; Katz, Michael

doi:10.1016/0165-1161(80)90193-4

Cited by 160 publications

(54 citation statements)

References 8 publications

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“…In recent years, this test has been utilized worldwide, both in vivo (using rodent and fish cells) and in vitro (using a range of cell types). Previous studies have demonstrated that plant extracts can induce the formation of a micronucleus during cell division through clastogenic (resulting in chromosome fragmentation caused by breaks) or aneugenic (resulting in the loss of whole chromosomes during cell division) actions (Salamone et al, 1980). During the telophase, these fragments or whole chromosomes are added to smaller nuclei known as "micronuclei", that are separate from the main nucleus (Kirsch-Volders et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

Assessment of the cytotoxic, genotoxic, and mutagenic potential of Acrocomia aculeata in rats

Traesel¹,

Castro²,

Silva³

et al. 2015

Genet. Mol. Res.

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ABSTRACT. Acrocomia aculeata (Jacq.) Lodd. ex Mart. is a plant species commonly used as a foodstuff and also for treating diseases, since it contains high concentrations of antioxidant compounds and monounsaturated fatty acids. Considering its ethnopharmacological relevance, the aim of the present study was to assess the cytotoxic, genotoxic, and mutagenic effects of an oil extracted from the pulp of A. aculeata (OPAC) in rats. In addition, a chromatographic characterization of the fatty acids present in OPAC was performed. Male and female Wistar rats were treated orally with 125, 250, 500, 1000, or 2000 mg/ kg/body weight OPAC. The effects of OPAC ingestion were determined by performing the comet assay and micronucleus test. The comet assay data demonstrated that OPAC did not increase the frequency or rate of DNA damage in groups treated with any of the concentrations assessed compared to that in the negative control group. In the micronucleus test, the animals treated did not exhibit any cytotoxic or mutagenic changes in peripheral blood erythrocytes. The results demonstrated that OPAC did not exhibit cytotoxic, genotoxic, or mutagenic effects in Wistar rats, thereby increasing the evidence for the safety of oil extracted from this plant.

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Section: Discussionmentioning

confidence: 99%

Assessment of the cytotoxic, genotoxic, and mutagenic potential of Acrocomia aculeata in rats

Traesel¹,

Castro²,

Silva³

et al. 2015

Genet. Mol. Res.

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“…3). The reason for this variation in the time of maximum response is not clear; we have speculated that it is related to the uptake and metabolism of the agent rather than any fundamental difference in the interaction with the bone marrow (6). The problem raised by this finding is that some agents may not produce detectable increases at 36 hr but are detectable at 72 hr.…”

mentioning

confidence: 41%

“…The problem raised by this finding is that some agents may not produce detectable increases at 36 hr but are detectable at 72 hr. Indeed a new protocol devised to take account of this possibility led to three carcinogens that were not detectable at early times being detected at later times (6). Because the results even at late times were marginal, this result needs to be confirmed.…”

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confidence: 91%

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Chromosomal aberrations and bone marrow toxicity.

Heddle¹,

Salamone²

1981

Environ Health Perspect

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The importance of chromosomal aberrations as a proximate cause of bone marrow toxicity is discussed. Since chemicals that can cause nondisjunction are rare, numerical aberrations (aneuploidy, polyploidy) are not ordinarily important. Many structural aberrations, however, can lead directly to cell death and so are proximate causes of toxicity when they occur. The micronucleus test which utilizes the polychromatic erythrocyte is capable of detecting agents (clastogens) that can cause such structural aberrations. Many carcinogens can be detected by this test, and recent changes in the protocol may increase the success rate. Nevertheless only a small proportion of chemicals are clastogens. The importance of cell division in the expression of chromosomal damage and the stage of the cell cycle at the time of exposure on the amount of damage is emphasized.A speculative mechanism for the relationship between chromosomal aberrations and carcinogenicity is proposed.There are two broad classes of chromosomal aberrations: numerical aberrations in which whole chromosomes are either lost or added, (e.g. trisomy-21 or Down's syndrome) and structural aberrations in which pieces of chromosome are lost, added, or translocated, for example the Philadelphia chromosome which leads to chronic myeloid leukemia.Obviously either class of aberration, if inherited, can have a significant influence on human health. These aberrations arise in fundamentally different ways. Aneuploidy, i.e., numerical aberrations involving other than a full complement of chromosomes, arise as a result of nondisjunction which is a failure of the proper distribution of chromosomes to daughter cells. Agents that interact directly with the cell's spindle mechanism are able to cause nondisjunction; there are also scattered reports which suggest that other agents may also be able to cause nondisjunction, perhaps by some indirect mechanism. Similarly, inhibition of the cell's spindle formation can lead to polyploidy, i.e., the gain or loss of whole haploid sets of chromosomes. In most tissues polyploid and aneuploid cells are rare Structural aberrations, in contrast, can lead directly to cell death and are often major contributors to toxicity. With respect to toxicity, the kinds of chromosomal aberrations (which from this point on in this paper means structural abnormalities except where otherwise indicated) may be classified in two ways: those that lead to the loss of genetic information at cell division and those that do not. This is shown diagrammatically in Figure 1. Those aberrations (of which only one of many possible types is shown) that involve a rearrangement of gene order rather than a direct loss of a gene are not cell lethal events and, hence, are not contributors to cellular toxicity. In contrast, those aberrations that lead directly to the loss of a section of genetic information are usually cell lethal events and do contribute directly to cellular toxicity. These aberrations may involve an acentric chromosomal fragment whose movement at anaphase is de...

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“…Five animals of each group were sacrificed 24 h after the treatment and the other five 48 h after the treatment. This protocol was chosen considering the observation that the time course of micronucleus production in polychromatic erythrocytes can be different for each of the chemicals studied (Salamone et al, 1980). The bone marrow from both femurs was flushed out using 2 mL saline (0.9% NaCl) and centrifuged for 7 min.…”

Section: Micronucleus Assaymentioning

confidence: 99%

Genotoxicity testing of Ambelania occidentalis (Apocynaceae) leaf extract in vivo

Castro

Perazzo²,

Maistro

2009

Genet. Mol. Res.

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ABSTRACT. Ambelania occidentalis is routinely used in folk medicine for treating gastrointestinal disorders, even though there have been no safety trials. We evaluated the genotoxic potential of hydro-alcoholic extracts of this plant in mice; induced DNA damage was assessed in peripheral blood leukocytes and micronucleus induction was assessed in polychromatic erythrocytes from bone marrow. The extract was administered by an oral route at single doses of 1000, 1500 and 2000 mg/ kg body weight. N-nitroso-N-ethylurea was used as a positive control. The comet assay was performed on peripheral blood leukocytes at 4 and 24 h after treatment, and the micronucleus test was carried out on bone marrow cells collected at 24 and 48 h after treatment. The ratio of polychromatic/normochromatic erythrocytes was scored for cytotoxicity assessment. No increase in the number of micronucleated polychromatic erythrocytes from bone marrow or in leukocyte DNA damage was observed. The hydro-alcoholic extracts of A. occidentalis had no mutagenic or cytotoxic effects in the mouse cells.

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Towards an improved micronucleus test Studies on 3 model agents, mitomycin C, cyclophosphamide and dimethylbenzanthracene

Cited by 160 publications

References 8 publications

Assessment of the cytotoxic, genotoxic, and mutagenic potential of Acrocomia aculeata in rats

Assessment of the cytotoxic, genotoxic, and mutagenic potential of Acrocomia aculeata in rats

Chromosomal aberrations and bone marrow toxicity.

Genotoxicity testing of Ambelania occidentalis (Apocynaceae) leaf extract in vivo

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