Mutagenicity tests with griseofulvin

Léonard, A.; Poncelet, F.; Grutman, G.; Carbonelle, E.; Fabry, L.

doi:10.1016/0165-1218(79)90154-x

Cited by 26 publications

(5 citation statements)

References 22 publications

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“…In a complementary study (data not shown) GF administered during a 3-week period in Sprague-Dawley male rats showed similar results. These data confirmed previous studies [15], indicating that the aneugenic effect observed in vitro, or in vivo in germ cells was not found, after in vivo exposure, in somatic cells which originate from the bone marrow.…”

Section: Discussionsupporting

confidence: 92%

“…Data on the induction of aneuploidy in vivo by GF in somatic cells are limited and conflicting. Leonard et al [15] obtained negative results in a mouse bone marrow micronucleus assay (500 to 2,000 mg/kg, intraperitoneal administration), whereas Aardema et al [16] showed that GF, administered orally at doses ranging from 2,000 to 5,000 mg/kg, induced significant increases in the frequency of micronucleated bone marrow cells.…”

Section: Introductionmentioning

confidence: 99%

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Effects of griseofulvin in medium‐term liver carcinogenesis assay and peripheral blood micronucleus test in rat

Labay

Ouldelhkim

Kles

et al. 2001

Teratog Carcinog Mutagen

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Published data have suggested a possible link between the tumor promoting activity and the aneugenic properties of griseofulvin. The present study was conducted to explore this relationship. Griseofulvin was evaluated both for its potential promoting activity in liver carcinogenesis in partially hepatectomized F344 male rats initiated by diethylnitrosamine and for its genotoxic potential in the peripheral blood micronucleus assay. Rats were treated daily with 2,000 mg/kg body weight by oral gavage for 12 weeks in the medium-term carcinogenesis bioassay. GST-P-positive foci (mean number and surface area) and altered cell foci were compared in the liver of rats treated with griseofulvin alone, diethylnitrosamine alone,and griseofulvin in addition to diethylnitrosamine by using immunohistochemical and histopathological evaluation, respectively. This evaluation allowed the conclusion that griseofulvin did not initiate the carcinogenic process but rather had a potential in the liver for tumor promoting activity. Griseofulvin was found to be negative in the rat peripheral blood micronucleus test when given at a daily oral dose of 2,000 mg/kg body weight for at least 3 weeks.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Effects of griseofulvin in medium‐term liver carcinogenesis assay and peripheral blood micronucleus test in rat

Labay

Ouldelhkim

Kles

et al. 2001

Teratog Carcinog Mutagen

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“…Griseofulvin has been tested in a number of assays for genotoxicity. In general, it has given negative results in tests for point mutations in bacterial systems, including the Ames test with strains of Salmonella typhimurium, and in a number of mammalian cell lines (Kuczuk et al, 1978;Leonard et al, 1979;Zimmerman et al, 1984;De Carli & Larizza, 1988;Zeiger et al, 1992). There is some limited evidence that griseofulvin is mutagenic in the mouse lymphoma TK + /TK ) L5178Y assay (Sofuni et al, 1996).…”

Section: Griseofulvinmentioning

confidence: 99%

“…In general, it has given negative results in tests for point mutations in bacterial systems, including the Ames test with strains of Salmonella typhimurium , and in a number of mammalian cell lines (Kuczuk et al. , 1978; Leonard et al. , 1979; Zimmerman et al.…”

Section: Introductionmentioning

confidence: 99%

Veterinary pharmacovigilance. Part 6. Predictability of adverse reactions in animals from laboratory toxicology studies

Woodward¹

2005

Vet Pharm & Therapeutics

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Toxicological studies are conducted on constituents of veterinary medicinal products for a number of reasons. Aside from being a requirement of legislation, they are carried out for predictive purposes in the assessment of user safety or for the determination of consumer safety, for example, in the elaboration of maximum residue limits or tolerances. Alternatively, the results of toxicology studies may be available as they have been generated for registration of the drug for human medicinal purposes. This paper examines if the results of such studies have any predictive value for adverse reactions, which might occur during clinical use in animals. A number of adverse reactions, notably the Type A (toxicology or pharmacology dependent) should be predictable from these laboratory studies. However, as with human pharmaceutical products, they have less utility in predicting Type-B reactions (idiosyncratic in nature).

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“…Although the assay has been studied extensively and is considered to be among the most popular in vivo assays for genotoxicity, it has led to discordant results, as reported in some studies for chemicals such as isoproturon (Behera and Bhunya, 1990;Gebez et al, 1997) and griseofulvin (Leonard et al, 1979;Aardema et al, 1996) number of other studies, the assay was inconclusive due to inadequate protocol designs (Mavournin et al, 1990). These results seem to indicate that the in vivo micronucleus assay suffers from a lack of robustness and sensitivity in some situations.…”

Section: Introductionmentioning

confidence: 99%

Application of pharmacokinetic/pharmacodynamic and stochastic modelling to 6‐mercaptopurine micronucleus induction in mouse bone marrow erythrocytes

Kles

Hyrien

Poul

et al. 2003

J of Applied Toxicology

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This study investigates the kinetics of bone marrow micronucleated polychromatic erythrocytes and some mechanistic aspects of micronuclei induction using mathematical models. Female mice were administered a single intraperitoneal injection of the purine antagonist 6-mercaptopurine at 50 mg kg(-1). The time course evolution of the drug concentrations in the plasma and the micronucleated polychromatic erythrocyte kinetic rate in bone marrow were observed. Two mathematical models were developed for this study. The first model was built from a simultaneous pharmacokinetic/pharmacodynamic approach, but was invalidated after comparing its predictions to experimental data. The second model was a stochastic model based on some biological hypotheses involved in micronuclei induction. This model predicted a wavy kinetic rate of micronucleated polychromatic erythrocytes that was confirmed by a second data set obtained from a specifically built experimental design. The biological hypotheses were then discussed. It turned out from this work that mathematical modelling could be used as a tool to explore the cellular mechanisms of toxicity of the compound: for instance, the assumptions that 6-mercaptopurine induced micronuclei mainly in cells entering the S phase, and not only during the last cell cycle but during one of the earlier cycles preceding the extrusion of the main nucleus, were confirmed. Moreover, the use of the stochastic model would help to schedule more accurately the bone marrow or blood harvesting times in the in vivo rodent micronucleus test.

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Mutagenicity tests with griseofulvin

Cited by 26 publications

References 22 publications

Effects of griseofulvin in medium‐term liver carcinogenesis assay and peripheral blood micronucleus test in rat

Effects of griseofulvin in medium‐term liver carcinogenesis assay and peripheral blood micronucleus test in rat

Veterinary pharmacovigilance. Part 6. Predictability of adverse reactions in animals from laboratory toxicology studies

Application of pharmacokinetic/pharmacodynamic and stochastic modelling to 6‐mercaptopurine micronucleus induction in mouse bone marrow erythrocytes

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