An evaluation of tests using DNA repair-deficient bacteria for predicting genotoxicity and carcinogenicity

Leifer, Zev; Kada, Tsuneo; Mandel, M.; Zeiger, Errol; Stafford, Robert; Rosenkranz, Herbert S.

doi:10.1016/0165-1110(81)90015-4

Cited by 84 publications

(19 citation statements)

References 59 publications

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“…Iron compounds have been reported to be mutagenic in mammalian culture cells, as detected by Syrian hamster embryo cell transformation/viral enhancement assay (Heidelberger et al 1983), base tautomerization in rat hepatocyte cultures (Abalea et al 1999) and genetic alterations in the mouse lymphoma assay (Dunkel et al 1999). However, negative results have also been reported, including from recombinational assay in DNA repair-deficient Bacillus subtilis (Leifer et al 1981), sister chromatic exchange in hamster cell culture (Tucker et al 1993), sex-linked recessive lethal gene mutation in Drosophila melanogaster (Lee et al 1983), gene mutation in Glycine max (Vig 1982) and tryptophan reverse gene mutation in Escherichia coli (Brusick et al 1980).…”

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confidence: 92%

“…In the same study, copper inhibited DNA repair. However, negative results have been observed in the recombinational assay in DNA repair-deficient B. subtilis (Leifer et al 1981), G. max gene mutation (Vig 1982) and mitotic recombination or gene conversion in Saccharomyces cerevisiae (Zimmermann et al 1984). An in vivo study by Saleha Banu et al (2004) in mice showed that, although copper genotoxicity demonstrated a clear dose-dependent response pattern, it gradually decreased from 48 h post-treatment, returning to the control levels 2 weeks after treatment.…”

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confidence: 95%

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Genotoxicity and mutagenicity of iron and copper in mice

et al. 2007

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The toxicity of trace metals is still incompletely understood. We have previously shown that a single oral dose of iron or copper induces genotoxic effects in mice in vivo, as detected by single cell gel electrophoresis (comet assay). Here, we report the effect of these metals on subchronic exposure. Mice were gavaged for six consecutive days with either water, 33.2 mg/kg iron, or 8.5 mg/kg copper. On the 7th day, the neutral and alkaline comet assays in whole blood and the bone marrow micronucleus (MN) test were used as genotoxicity and mutagenicity endpoints, respectively. Particle induced X-ray emission was used to determine liver levels of the metals. Females showed a slightly lower DNA damage background, but there was no significant difference between genders for any endpoint. Iron and copper were genotoxic and mutagenic. While copper was more genotoxic in the neutral version, iron was more genotoxic in the alkaline version of the comet assay. Copper induced the highest mutagenicity as evaluated by the MN test. Iron was not mutagenic to male mice. Iron is thought to induce more oxidative lesions than copper, which are primarily detected in the alkaline comet assay. Treatment with iron, but not with copper, induced a significant increase in the hepatic level of the respective metal, reflecting different excretion strategies.

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confidence: 92%

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confidence: 95%

Genotoxicity and mutagenicity of iron and copper in mice

et al. 2007

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“…When mutagenic activity was assessed in bacterial systems with the Salmonella typhimurium Ames test either positive or negative results have been reported (Simmon, 1979;Plewa et al, 1984;Kier et al, 1986). Furthermore, similar situation were observed in Escherichia coli and Bacillus subtilis when the reverse mutation assay was applied (Simmon, 1979;Leifer et al, 1981;Waters et al, 1981). Whereas the herbicide was unable to induce mitotic recombination in Saccharomyces cerevisiae (Zimmermann et al, 1984), negative and positive results were obtained for the induction of unscheduled DNA synthesis in human primary cells regardless of the presence or absence of a rat liver metabolic activation system (Simmon, 1979;Perocco et al, 1990).…”

Section: Genotoxicity and Cytotoxicity Of Dicambamentioning

confidence: 71%

Herbicides in Argentina. Comparative Evaluation of the Genotoxic and Cytotoxic Effects on Mammalian Cells Exerted by Auxinic Members

Soloneski¹,

Larramendy²

2011

Herbicides and Environment

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“…In the present work we used a suspension procedure of the DNArepair test to evaluate the DNA-damaging potency of the test compound (Leifer et al 1981;McCarroll et al 1981). The tester strains of Escherichia coli WP2 (trpE65; repair-proficient) and strains defective in excision repair (uvrA; trpE65 uvrA155) or in recombination capacity (recA; trpE65 recA) were obtained from the Scientific Research Institute of Genetics (Moscow, Russia).…”

Section: Bacterial Dna-repair Testmentioning

confidence: 99%

Genotoxicity study of a new tetraalkylammonium derivative of 6-methyluracil (agent No. 547)

Karamova

Ivanchenko

Ilinskaya

et al. 2002

Archives of Toxicology

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Agent No. 547 (1,3-bis[omega-(diethyl-ortho-nitrobenzylammonio)-pentyl]-6-methyluracil dibromide), a newly synthesized inhibitor of mammalian-specific acetyltcholinesterase (EC 3.1.1.7) was investigated for genotoxicity using the DNA-repair test, Ames test and in vivo micronucleus test with mouse peripheral blood erythrocytes. Agent No. 547 did not cause significant changes in growth of repair-deficient Escherichia coli tester strains. The compound was non-mutagenic in Salmonella typhimurium strains TA98 and TA100 with and without rat microsomal activation mixture. However, we observed a marked increase in number of His(+) revertants for both tester strains in preincubation assays. The results obtained in the micronucleus test indicate that agent No. 547 possesses significant clastogenic activity. At the high dose tested (0.5 mg/kg), the compound induced a seven-fold increase in the number of micronuclei over the spontaneous background 48 h after treatment. The results suggest that further work should be promoted to identify the metabolic pathways involved in genotoxicity of agent No. 547 in mammalian cells and to evaluate the real risk of its exposure.

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An evaluation of tests using DNA repair-deficient bacteria for predicting genotoxicity and carcinogenicity

Cited by 84 publications

References 59 publications

Genotoxicity and mutagenicity of iron and copper in mice

Genotoxicity and mutagenicity of iron and copper in mice

Herbicides in Argentina. Comparative Evaluation of the Genotoxic and Cytotoxic Effects on Mammalian Cells Exerted by Auxinic Members

Genotoxicity study of a new tetraalkylammonium derivative of 6-methyluracil (agent No. 547)

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