Aspects of chloroquine mutagenicity

Obaseiki-Ebor, Emmanuel E.; Obasi, E. E.

doi:10.1016/0165-7992(86)90125-9

Cited by 16 publications

(18 citation statements)

References 15 publications

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“…Similar results were reported with other bacterial strains, including Escherichia coli strains EE97 and EE102 [Obaseiki-Ebor and Obasi, 1986], E. coli pol A ϩ /pol A Ϫ strains [Espinosa-Aguirre et al, 1987], and E. coli strain DG1669 [Thomas et al, 1987]. Mutagenicity was essentially identical with wild-type, recA, umuC, and uvrC strains of DG1669, as well as with strains carrying the mutationenhancing plasmid pKM101, suggesting that neither excision repair nor SOS-type repair is important in CQ-induced frameshift mutagenesis [Thomas et al, 1987].…”

Section: Introductionsupporting

confidence: 83%

“…These two tester strains are both sensitive to frameshift mutagens; however, they revert at different sites (hisC3076 and hisD3052, respectively). Previous reports demonstrated the mutagenicity of CQ in a variety of tester strains, including S. typhimurium strains TA97a, TA98, TA100, TA104, and TA1537 [Cortinas de Nava et al, 1983;Obaseiki-Ebor and Obasi, 1986;Thomas et al, 1987;Chatterjee et al, 1998] and E. coli strains EE97, Thomas et al, 1987]; however, these positive results are generally based on two-to threefold increases in mutations, and responses in individual strains were not reproducible between laboratories. The lack of reproducibility between laboratories suggests that CQ and AQ-13 are, at best, very weak bacterial mutagens.…”

Section: Discussionmentioning

confidence: 76%

“…CQ was positive for mutagenicity with tester strain TA1537 [Cortinas de Nava et al, 1983], whereas mefloquine did not induce mutagenicity at concentrations up to 2.5 g/ml, either without or with MA [Schupbach, 1979]. CQ was previously reported to be mutagenic with strains TA98 and TA97 [Obaseiki-Ebor and Obasi, 1986;Thomas et al, 1987].…”

Section: Introductionmentioning

confidence: 89%

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Genetic toxicology testing of the antimalarial drugs chloroquine and a new analog, AQ‐13

Riccio

Lee

Winegar

et al. 2001

Environ and Mol Mutagen

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AQ-13 ([N1-(7-chloro-quinolin-4yl)-3-(N3,N3-diethylamino)propylamine] dihydrochloride trihydrate) is an aminoquinoline antimalarial drug that is effective against chloroquine-resistant strains of Plasmodium falciparum. It is structurally similar to the widely used chloroquine diphosphate (CQ). We evaluated these drugs in the three assays currently recommended by the International Conference on Harmonization (ICH): bacterial mutagenesis in Salmonella typhimurium and Escherichia coli, mammalian cell mutagenesis in L5178Y mouse lymphoma cells, and micronucleus induction in rat bone marrow. A small but statistically significant increase in revertant colonies was produced by CQ with Salmonella tester strain TA98 without metabolic activation (MA) and by AQ-13 with strain TA1537 both with and without MA. In L5178Y cells, testing of CQ and AQ-13 up to cytotoxic concentrations with and without MA produced no increase in mutant colonies and no increase in the numbers of small colonies. Slight decreases in the ratio of polychromatic erythrocytes (PCE) to red blood cells (RBC) were observed in male and female rats treated with CQ and in females only treated with AQ-13; however, none of these changes was statistically significant. No increases in the frequency of micronucleated PCE were observed at any dose level of CQ or AQ-13. Although both CQ and AQ-13 showed weak bacterial mutagenicity, this mutagenic effect was not confirmed in either the mouse lymphoma mutagenesis assay or the micronucleus assay. These results indicate that CQ and AQ-13 should pose minimal risk of genotoxic damage in human populations being administered these drugs.

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Section: Introductionsupporting

confidence: 83%

Section: Discussionmentioning

confidence: 76%

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Genetic toxicology testing of the antimalarial drugs chloroquine and a new analog, AQ‐13

Riccio

Lee

Winegar

et al. 2001

Environ and Mol Mutagen

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“…The lack of therapeutic options, the resistance of Plasmodium to the available drugs (Gasquet et al, 1995;Longworth, 1995;Blair et al, 1999Blair et al, , 2001aBlair et al, , 2002 and the toxicity and mutagenic potential of some of these drugs (Obaseiki-Ebor and Obasi, 1986;Thomas et al, 1987) have motivated us to search for new therapeutic alternatives among plants used as antimalarials by traditional healers for the treatment of this disease (Makinde et al, 1987;Brandao et al, 1992;Weniger et al, 2001). One of these plants is Solanum nudum Dunal (Solanaceae) which is used for that purpose in the Tumaco region (Southwest of Colombia) (Saez and Espinal, 1994;Saez et al, 1998;Echeverry et al, 2001;Pabón et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Evaluation of clastogenic potential of the antimalarial plant Solanum nudum

Álvarez

Pabón

Carmona

et al. 2004

Phytotherapy Research

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Compounds isolated from Solanum nudum have shown in vitro antimalarial activity against the FCB-2 strain of Plasmodium falciparum. Diosgenone (C27H40O3) the main component isolated from the hexane extract and an aqueous extract were evaluated to measure their clastogenic potential using the micronucleus test. Three concentrations (16, 32 and 64 g/kg of weight) of the aqueous extract were administered intraperitoneally into mice, (the highest concentration corresponded to 80% LD50) and diosgenone solubilized in olive oil was inoculated at the highest concentration possible (11.187 g/kg of weight). After administration of the compounds, no induction of micronucleus was observed either in polychromatic or normochromatic erythrocytes. Interestingly, a reduction of 51% in the young/mature erythrocytes ratio was seen in cells treated with aqueous extract. We conclude that neither diosgenone nor the aqueous extract have clastogenic activity, and that the aqueous extract showed some toxicity at the above mentioned concentrations. These results are significant since diosgenone could be a new therapeutic alternative for the treatment of malaria.

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“…Ebor et al, 23 used Ames plate reversion and fluctuation tests to evaluate the mutagenic and genotoxic potentials of chloroquine using different strains of Salmonella typhimurium and Escherichia coli. The results indicated that chloroquine had a potential to cause frame shift mutation.…”

Section: Structure Of Chloroquinementioning

confidence: 99%

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2012

IJPSR

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Aspects of chloroquine mutagenicity

Cited by 16 publications

References 15 publications

Genetic toxicology testing of the antimalarial drugs chloroquine and a new analog, AQ‐13

Genetic toxicology testing of the antimalarial drugs chloroquine and a new analog, AQ‐13

Evaluation of clastogenic potential of the antimalarial plant Solanum nudum

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