Evaluating statistical analyses and reproducibility of microbial mutagenicity assays

Chu, Kenneth C.; Patel, K.M.; Lin, An-loh; Tarone, Robert E.; Linhart, M.S.; Dunkel, Virginia C.

doi:10.1016/0165-1161(81)90027-3

Cited by 140 publications

(41 citation statements)

References 4 publications

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“…In order to progress in the lead optimization discovery stage, the different potential toxic effects of the best-developed compounds were analyzed. In this sense, in vitro mutagenicity was analyzed using the method of direct incubation in a plate of Salmonella Typhimurium cultures (18,19). In contrast to the reference drugs, Bnz and Nfx, all the new compounds were not mutagenic against the TA98 strain of S. Typhimurium (see Table S3 in the supplemental material).…”

Section: Resultsmentioning

confidence: 99%

“…For the mutagenicity assay (18)(19)(20)(21)(22), the method of direct incubation in the plate was performed. Culture of Salmonella enterica serovar Typhimurium TA98, TA100, TA102, TA1535, and TA1537 strains in the agar minimum glucose medium-agar solution, 50ϫ Vogel-Bonner E, and 40% glucose solution was used.…”

Section: Syntheses Of New Thiazole Derivatives (Compounds 3 To 11)mentioning

confidence: 99%

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Identification of a New Amide-Containing Thiazole as a Drug Candidate for Treatment of Chagas' Disease

Álvarez

Varela

Cruces

et al. 2015

Antimicrob Agents Chemother

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Although the parasitic infection Chagas' disease was described over 100 years ago, even now there are not suitable drugs. The available drugs nifurtimox and benznidazole have limited efficacies and tolerances, with proven mutagenic effects. Attempting to find appropriate drugs to deal with this problem, here we report on the development and pharmacological characterization of new amide-containing thiazoles. In the present study, we evaluated the in vitro and in vivo effects of new candidates against Trypanosoma cruzi, the etiological agent of Chagas' disease. The lead amide-containing thiazole derivative had potent in vitro activity, an absence of both in vitro mutagenic and in vivo clastogenic effects, and excellent in vitro selectivity and in vivo tolerance. The compound suppressed parasitemia in mice, modifying the anti-T. cruzi antibodies like the reference drug, benznidazole, and displayed the lowest mortality among the tested drugs. The present evidence suggests that this compound is a promising anti-T. cruzi agent surpassing the lead optimization stage in drug development and leading to a candidate for preclinical study.

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Section: Resultsmentioning

confidence: 99%

Section: Syntheses Of New Thiazole Derivatives (Compounds 3 To 11)mentioning

confidence: 99%

Identification of a New Amide-Containing Thiazole as a Drug Candidate for Treatment of Chagas' Disease

Álvarez

Varela

Cruces

et al. 2015

Antimicrob Agents Chemother

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“…The results were analyzed using the 2-fold rule (Chu et al, 1981) in which a response is considered positive if the mean frequency values were more than twice the spontaneous frequencies and were subjected to multifactor analysis of variance with computer assistance (Statgraphics 4.0).…”

Section: Interpretation Of Resultsmentioning

confidence: 99%

Bleomycin genotoxicity alteration by glutathione and cytochrome P-450 cellular content in respiratory proficient and deficient strains of Saccharomyces cerevisiae

et al. 1999

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The genotoxic effects of the antiblastic drug bleomycin were studied in the D7 strain of Saccharomyces cerevisiae and on its derivative mitochondrial mutant ρ°at different cellular concentrations of two drug metabolizing systems, glutathione (GSH) and cytochrome P-450. Bleomycin mutagenic activity was evaluated as frequencies of mitotic gene conversion, reversion and total aberrations under different physiological conditions. In the D7 strain, petite mutant induction was also detected. This is important due to the role of the mitochondrial genome in cancer induction, ageing and degenerative diseases. Both strains showed higher convertant than revertant induction. At high cytochrome P-450 levels, bleomycin-induced gene conversion was enhanced in both strains although mitochondrial functionality showed a detoxicant role while cellular GSH content decreased the induction of convertants only in the respiratory proficient strain. Cell metabolic conditions, such as cell cycle, aerobic/hypoxic conditions of the cell and content of drug metabolizing enzymes, appeared to interact with the genotoxic effectiveness of bleomycin. Moreover, the usefulness of S.cerevisiae as a model organism for drug assessment for mutagenicity was emphasized.

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“…There are different statistical approaches: One can ignore the muta-tox problem; this strategy is frequent in praxi. Another pragmatic method is to reject high doses before testing (5). A transformation can moderate the muta-tox problem.…”

Section: Markus Neuhauser and Ludwig A Hothornmentioning

confidence: 99%

The Control of The Consumer Risk in the Ames Assay

Neuhäuser

Hothorn

1997

Drug Information J

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Preclinical tests in genetic toxicology represent safety studies. Therefore, the primary concern in the evaluation of Ames test data is the control of the consumer risk, that is, the risk of erroneously concluding safety. Hence, an equivalence test procedure is adequate. This approach is presented beside the two-fold rule and classical tests for differences with respect to an order restricted alternative.

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Evaluating statistical analyses and reproducibility of microbial mutagenicity assays

Cited by 140 publications

References 4 publications

Identification of a New Amide-Containing Thiazole as a Drug Candidate for Treatment of Chagas' Disease

Identification of a New Amide-Containing Thiazole as a Drug Candidate for Treatment of Chagas' Disease

Bleomycin genotoxicity alteration by glutathione and cytochrome P-450 cellular content in respiratory proficient and deficient strains of Saccharomyces cerevisiae

The Control of The Consumer Risk in the Ames Assay

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