System issues: Evaluation of the in vivo genotoxic potential of three carcinogenic aromatic amines using the Big Blue™ transgenic mouse mutation assay

Suter, Willi; Ahiabor, R.; Blanco, B.; Locher, Franziska; Mantovani, Fiamma; Robinson, Merrel; Sreenan, G.; Staedtler, Frank; Swingler, T.E.; Vignutelli, A.; Perentes, Elias

doi:10.1002/(sici)1098-2280(1996)28:4<354::aid-em9>3.0.co;2-b

Cited by 28 publications

(6 citation statements)

References 38 publications

(17 reference statements)

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“…2,4-DAT induces DNA damage (comets) in the mouse liver, while 2,6-DAT does not (18). 2,4-DAT induces LacI, LacZ and gpt mutations in the liver of Big Blue TM mice (19,20), Muta TM Mouse transgenic mice (21) and F344 gpt delta transgenic rats (6), respectively, while 2,6-DAT does not (6,20,21). Both 2,4-DAT and 2,6-DAT weakly induce micronuclei in rat bone marrow (22), while neither 2,4-DAT nor 2,6-DAT in peripheral blood of F344 gpt delta transgenic rat (6).…”

supporting

confidence: 87%

“…In particular, the results of TGR assays using the liver are correlated with those of the bioassays for carcinogenicity of 2,4-DAT and 2,6-DAT; however, the MF is not increased when the treatment period (19) and the sampling time (20) are not appropriate. Thus, the treatment period and the sampling time are important factors in the TGR assay protocol.…”

mentioning

confidence: 99%

“…This negative result was consistent with the results of carcinogenicity study (8) and the other in vivo genotoxicity assays (6,(17)(18)(19)(20)(21). However, weakly positive result of 2,6-DAT in the rat bone marrow micronucleus study is present (22).…”

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confidence: 99%

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Evaluation of In Vivo Mutagenicity by 2,4-Diaminotoluene and 2,6-Diaminotoluene in Liver of F344 gpt delta Transgenic Rat Dosed for 28 Days: A Collaborative Study of the gpt delta Transgenic Rat Mutation Assay

Sui

Ohta

Shiragiku

et al. 2012

Genes and Environment

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The transgenic rodent (TGR) assay has been widely used to study in vivo gene mutations by chemicals or radiation; however, an optimal protocol has not yet been established to assess unknown genotoxic potential. The International Workshop on Genotoxicity Testing (IWGT) strongly recommends a repeated-dose regimen for the TGR assay protocol for regulatory safety assessment as follows: a treatment period of 28 days and a sampling time of 3 days following theˆnal treatment. In this study, TGR assays using F344 gpt delta transgenic rats were conducted at three laboratories to evaluate the validity of the IWGT protocol, as part of a collaborative study of the transgenic rat mutation assay. Male F344 gpt delta transgenic rats were orally treated with 2,4-diaminotoluene (2,4-DAT; hepatic carcinogen in rodents; 10 and 30 mg/kg/day) or 2,6-diaminotoluene (2,6-DAT; non-carcinogen in rodents; 60 mg/ kg/day) once daily for 28 days. Rats were euthanized 3 days after the last dosing, and then mutant frequencies (MFs) of the gpt gene in the livers were studied. As a result, a signiˆcant increase in the MF was observed at 30 mg/kg in the 2,4-DAT-treated group, but not in the 2,6-DAT-treated group. These results were commonly observed among the three laboratories. In addition, the overall results from the three laboratories were in general agreement. These results indicate that 2,4-DAT induces gene mutation in the liver of gpt delta rats, but 2,6-DAT does not. These results also indicate that the F344 gpt delta transgenic rat mutation assay can distinguish diŠer-ences in the in vivo mutagenic potential between a hepatic carcinogen and a non-carcinogen. Results from one laboratory showed more variability than those from the other two laboratories, and this appearance was due to the smaller number of colonies scored. Thus, these results demonstrate that the IWGT protocol for the TGR assays is valid, and show that consistent results are obtained among diŠerent laboratories.

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confidence: 87%

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confidence: 99%

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Evaluation of In Vivo Mutagenicity by 2,4-Diaminotoluene and 2,6-Diaminotoluene in Liver of F344 gpt delta Transgenic Rat Dosed for 28 Days: A Collaborative Study of the gpt delta Transgenic Rat Mutation Assay

Sui

Ohta

Shiragiku

et al. 2012

Genes and Environment

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“…From the studies by Mann [1], Barnes [42] and Smith [43] on the electrochemical oxidation of primary amines and from previous studies we made on the electrochemical oxidation of aliphatic diamines [24,25], we took the anodic oxidation of pPD the mechanism described in Figure 9. The first step is the adsorption of pPD on the surface electrode.…”

Section: Discussionmentioning

confidence: 99%

Chemical and Biological Analyses of the Role of the Poly- Para- Phenylenediamine in the Erythrocytes Resistance in Hypotonic Environment

Srhayri¹,

Naimi²,

Takky³

et al. 2016

J Membra Sci Technol

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potential scan rate of 200 mVs-1, two voltametric waves on the platen; which corresponds to two successive and reversible processes to a single electron, leading to the formation of a diamine [24].Moreover, the genotoxicity studies in vitro have shown that pPD, like several other aromatic amines which belong to the aniline family can react with DNA and cause breaks . Picardo et al. have shown that pPD at high concentrations and for long exposure time induced cell cycle block and toxicity, but at low concentrations (10 µg/mL)and for shorter periods exposure (30 min) increased keratinocyte proliferation [39]. Habti et al. [6] have shown that pPD at low concentrations (5µg/mL) and for 2h exposure time gives RBC temporary resistance to hemolysis in hypotonic blend, the mechanism remains unexplained till now [6]. The aim of our study is to contribute to elucidate the molecular mechanism responsible for this temporary resistance. Material and Methods Collection of human blood sampleBlood samples from volunteer donors, and healthy aged 25-35 years were collected in tubes of 7 mL containing EDTA. Blood donors were nonsmokers and had no history of allergic reaction to pPD or AbstractThe high chemical and biological reactivity of para-phenylenediamine (pPD) has been illustrated in several studies, including polymerization genotoxicity and oxidative stress at the level of the plasma membrane cells. However, its reactivity with red blood cells (RBC) was rarely explored.The aim of this study is to help expound the molecular actions of para-phenylenediamine in hypotonic environment of human red blood cells by conducting biological tests for the globular resistance and physicochemical cyclic voltammetry and UV-visible spectroscopy.Our results show that the para-phenylenediamine at low concentration gives red blood cells temporary resistance (30 min) against hemolysis in hypotonic environment with 4.5 g/L NaCl. Spectrometry results for UVvisible and cyclic voltammetry suggest that membrane stability is due to the presence of the polymer poly-paraphenylenediamine (poly-pPD).

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“…4-Cl-o-PDA itself is found to be mutagenic [13][14][15] and genotoxic through standard in vitro assays [16,17]. It is mutagenic and a liver carcinogen in big blue mice [18][19][20], and induces hepatocellular carcinomas in both sexes of mice and tumors of the urinary bladder [14]. 4-Cl-o-PDA is not mutagenic in Salmonella typhimurium bacteria strain TA 98 in the presence of the S9 mix, but its oxidation products show mutagenicity [21].…”

Section: Introductionmentioning

confidence: 99%

Photochemical reaction of a dye precursor 4-chloro-1,2-phenylenediamine and its associated mutagenic effects

Wang

Mosley

Stewart

et al. 2008

Journal of Photochemistry and Photobiology A: Chemistry

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System issues: Evaluation of the in vivo genotoxic potential of three carcinogenic aromatic amines using the Big Blue™ transgenic mouse mutation assay

Cited by 28 publications

References 38 publications

Evaluation of In Vivo Mutagenicity by 2,4-Diaminotoluene and 2,6-Diaminotoluene in Liver of F344 gpt delta Transgenic Rat Dosed for 28 Days: A Collaborative Study of the gpt delta Transgenic Rat Mutation Assay

Evaluation of In Vivo Mutagenicity by 2,4-Diaminotoluene and 2,6-Diaminotoluene in Liver of F344 gpt delta Transgenic Rat Dosed for 28 Days: A Collaborative Study of the gpt delta Transgenic Rat Mutation Assay

Chemical and Biological Analyses of the Role of the Poly- Para- Phenylenediamine in the Erythrocytes Resistance in Hypotonic Environment

Photochemical reaction of a dye precursor 4-chloro-1,2-phenylenediamine and its associated mutagenic effects

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