Effects of high doses of vitamins C and E against doxorubicin-induced chromosomal damage in Wistar rat bone marrow cells

Antunes, Lusânia Maria Greggi; Takahashi, Catarina Satie

doi:10.1016/s1383-5718(98)00134-x

Cited by 87 publications

(52 citation statements)

References 36 publications

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“…According to Halliwell (2001) AA, a water-soluble glucose derivative, has considerable antioxidant activity in vitro, in part because of its ease of oxidation and because the semidehydroascorbate radical derived from it is of low reactivity, but there are conflicting effects of AA reported on the induction of DNA strand breaks, micronuclei and frequency of chromosomal aberrations. It has been previously reported that AA successfully inhibited the chromosome aberrations induced by DXR in rat bone marrow cells (Antunes and Takahashi, 1998), micronuclei in cytokinesis-blocked human lymphocytes and the chromosomal aberration assay in V79 Chinese hamster cells induced by the mycotoxin patulin (Alves et al, 2000) and mercury-induced genotoxicity in human blood cultures (Rao et al, 2001). However, administration of high doses of AA appears to have mutagenic effects in different test systems.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, a significant reduction in total plasma antioxidant capacity was observed in smallcell lung cancer patients treated with DXR (Erhola et al, 1996). It is important to reduce the genotoxicity of DXR in non-tumor cells, a goal that has been achieved experimentally by concurrent administration of free radical scavengers such as antioxidants (Amara-Mokrane et al, 1996;Antunes and Takahashi, 1998;Gentile et al, 1998;Costa and Nepomuceno, 2006;Antunes et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

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Modulatory effects of the antioxidant ascorbic acid on the direct genotoxicity of doxorubicin in somatic cells of Drosophila melanogaster

2007

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In this study two different crosses involving the wing cell markers mwh and flr 3 (standard (ST) cross and high bioactivation (HB) cross, the latter being characterized by a high constitutive level of cytochrome P450 which leads to an increased sensitivity to a number of promutagens and procarcinogens) were used to investigate the modulatory effects of ascorbic acid (AA) combined with the antitumor agent doxorubicin (DXR) in Drosophila melanogaster. We observed that the two different concentrations of AA (50 or 100 mM) had no effect on spots frequencies, while DXR treatments (0.2 or 0.4 mM) gave positive results for all types of spots, when compared to negative control. For marker-heterozygous (MH) flies, a protective effect was observed with the lower concentration of AA (50 mM) that was able to statistically decrease the frequency of spots induced by DXR (0.2 mM), while an enhanced frequency of spots induced by DXR was observed with the higher concentration of AA (100 mM), when compared to DXR treatment (p < 0.05). These results suggest that AA may interfere with free radicals generated by DXR and with other possible reactive metabolites. The efficiency of AA in protecting the somatic cells of D. melanogaster against mutation and recombination induced by DXR is dependent on the dose used and the protection is directly related to the activity of cytochrome P450 enzymes.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Modulatory effects of the antioxidant ascorbic acid on the direct genotoxicity of doxorubicin in somatic cells of Drosophila melanogaster

2007

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“…The main mechanisms of action proposed for DOX include the inhibition of topoisomerase II, DNA intercalation, free radical formation, reductive bioactivation of the quinine ring to a semiquinone radical, DNA alkylation and cross-linking (Gewirtz, 1999;Ramji et al, 2003;Navarro et al, 2006). These mechanisms can result in the cleavage of DNA which, if not repaired, may lead to mutations and chromosomal aberrations in tumors as well as in healthy cells (Antunes and Takahashi, 1998;Gentile et al, 1998;Islaih et al, 2005;Antunes et al, 2007;Costa and Nepomuceno, 2006;Fragiorge et al, 2007;Valadares et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Protection by Panax ginseng C.A. Meyer against the genotoxicity of doxorubicin in somatic cells of Drosophila melanogaster

et al. 2008

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Panax ginseng is one of the most widely prescribed herbal medicines for the treatment of cancer, diabetes, chronic inflammation, and neurodegenerative and cardiovascular diseases. Since the use of alternative medicines in combination with conventional therapy may increase the risk of unwanted interactions, we investigated the possible genotoxicity of a water-soluble form of the dry root of P. ginseng (2.5, 5.0 or 10.0 mg/mL) and its ability to protect against the genotoxicity of doxorubicin (DOX; 0.125 mg/mL) by using the Drosophila melanogaster wing somatic mutation and recombination test (SMART) with standard and high-bioactivation crosses of flies. Panax ginseng was not genotoxic at the concentrations tested, whereas DOX-induced genotoxicity in marker-heterozygous flies resulted mainly from mitotic recombination. At low concentrations, P. ginseng had antirecombinogenic activity that was independent of the concentration of extract used. Recombination events may promote cancer, but little is known about the ability of P. ginseng to inhibit such recombination or modulate DNA repair mechanisms.

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“…Doxorubicin (DXR) is an important chemotherapeutic agent that induces cardiotoxicity, as well as chromosome aberrations. It is important to reduce its toxicity in normal cells, a goal that can be achieved by concurrent administration of free radical scavenging agents, such as antioxidants (Amara-Mokrane et al, 1996;Matsuda et al, 1997;Antunes and Takahashi, 1998). The present study was undertaken to investigate the modulatory effect of the simultaneous treatment with olive oil, a dietary antioxidant, on the clastogenic action of DXR in Wistar rat bone marrow cells.…”

Section: Introductionmentioning

confidence: 99%

Olive oil protects against chromosomal aberrations induced by doxorubicin in wistar rat bone marrow cells

Antunes¹,

Takahashi²

1999

Genet. Mol. Biol.

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There is considerable interest in identifying dietary compounds which have the capacity to protect against chromosomal aberrations induced by antitumor agents. Fatty acids and their constituents are able to act as free radical scavengers. Doxorubicin (DXR) is an important chemotherapeutic agent, that also induces chromosome aberrations. Rat bone marrow cells treated simultaneously with olive oil (10 ml/kg body weight) and DXR (90 mg/kg body weight) developed significantly fewer chromosomal aberrations and abnormal metaphases than those treated with DXR alone.
Existe considerável interesse na identificação de componentes da dieta que têm a capacidade de proteger contra as aberrações cromossômicas induzidas pelos agentes antitumorais. Os ácidos graxos e seus constituintes são capazes de atuar como seqüestradores de radicais livres. Na presente investigação, as células da medula óssea dos animais tratados simultaneamente com o óleo de oliva (10 ml/kg de peso corporal) e doxorubicina (DXR; 90 mg/kg de peso corporal) apresentaram uma significativa redução no total de aberrações cromossômicas e metáfases alteradas induzidas pela DXR

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Effects of high doses of vitamins C and E against doxorubicin-induced chromosomal damage in Wistar rat bone marrow cells

Cited by 87 publications

References 36 publications

Modulatory effects of the antioxidant ascorbic acid on the direct genotoxicity of doxorubicin in somatic cells of Drosophila melanogaster

Modulatory effects of the antioxidant ascorbic acid on the direct genotoxicity of doxorubicin in somatic cells of Drosophila melanogaster

Protection by Panax ginseng C.A. Meyer against the genotoxicity of doxorubicin in somatic cells of Drosophila melanogaster

Olive oil protects against chromosomal aberrations induced by doxorubicin in wistar rat bone marrow cells

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