Frameshift mutagenesis by chloroquine in Escherichia coli and Salmonella typhimurium

Thomas, Susan M.; Silburn, Katherine A.; MacPhee, Donald G.

doi:10.1016/0165-7992(87)90062-5

Cited by 15 publications

(14 citation statements)

References 13 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: 80%

“…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%

“…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: Introductionmentioning

confidence: 97%

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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: 80%

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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“…Chloroquine have been reported to be weakly mutagenic in Salmonella typhimurium by Ames and Whitfield 30 and Thomas et al 31 . Mutagenic potential of the drug was also evaluated by Kadotani et al 32 in Bacillus subtilis and similar result was reported.…”

Section: Structure Of Chloroquinementioning

confidence: 99%

“…Potential of chloroquine to cause frameshift mutation in different strains of Salmonella typhimurium and E. coli with rat liver S9 was studied by Thomas et al 24 . The result of the test suggested that chloroquine induces frame shift mutagenesis.…”

Section: Structure Of Chloroquinementioning

confidence: 99%

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2012

IJPSR

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Mutagenic activity and mutational specificity of antiprotozoal drugs with and without nitrite treatment

Ono-Ogata¹,

Ogino²,

Nishikawa³

et al. 2002

Environ and Mol Mutagen

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We examined the mutagenic activities of six antiprotozoal drugs (three diaminopyrimidine compounds [pyrimethamine, diaveridine, and trimethoprim] and three 8-aminoquinoline derivatives [primaquine, pentaquine, and pamaquine]) in Escherichia coli WP2uvrA/pKM101 and Salmonella typhimurium TA100 and TA98 with and without nitrite treatment. The diaminopyrimidine compounds showed no mutagenic activity under any condition in any strain. The 8-aminoquinoline derivatives after nitrite treatment at 5-20 mM for 5 min at pH 3, on the contrary, showed clear mutagenicity in TA100 and WP2uvrA/pKM101 in the presence and absence of S9 mix. We concluded that 8-aminoquinoline derivatives became mutagenic following nitrite treatment. In the Lac(+) reversion assay with E. coli WP3101P-WP3106P, these nitrite-treated compounds induced G:C --> A:T transitions and G:C --> T:A transversions in the absence of S9 mix. On the other hand, A:T --> T:A transversions were induced only in the presence of S9 mix, suggesting a different kind of products may be responsible for the mutagenicity.

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Frameshift mutagenesis by chloroquine in Escherichia coli and Salmonella typhimurium

Cited by 15 publications

References 13 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

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Mutagenic activity and mutational specificity of antiprotozoal drugs with and without nitrite treatment

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