Carcinogenicity of orthoaminoazotoluene for the mouse intestines

Каледин, В. И.; Alekseeva, Galina V.; Volkova, Anna I.

doi:10.1007/bf00800463

Cited by 4 publications

(4 citation statements)

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“…Since that time, a large amount of data has confirmed the carcinogenic activity of azo dyes. Specifically, OAT is known as a mouse carcinogen (Kaledin et al, 1978; Kaledin et al, 1985), and has been evaluated by the International Agency for Research on Cancer (IARC) as a possible (class 2B) human carcinogen (IARC, 1975; National Toxicology Program, 2002). Despite more than a half a century of studies on OAT induced carcinogenesis, its mechanism of action is still unknown.…”

Section: Introductionmentioning

confidence: 99%

Ortho-aminoazotoluene activates mouse constitutive androstane receptor (mCAR) and increases expression of mCAR target genes

Сметанина

Pakharukova

Kurinna

et al. 2011

Toxicology and Applied Pharmacology

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2'-3-dimethyl-4-aminoazobenzene (ortho-aminoazotoluene, OAT) is an azo dye and a rodent carcinogen that has been evaluated by the International Agency for Research on Cancer (IARC) as a possible (class 2B) human carcinogen. Its mechanism of action remains unclear. We examined the role of the xenobiotic receptor Constitutive Androstane Receptor (CAR, NR1I3) as a mediator of the effects of OAT. We found that OAT increases mouse CAR (mCAR) transactivation in a dose-dependent manner. This effect is specific because another closely related azo dye, 3'-methyl-4-dimethyl-aminoazobenzene (3'MeDAB), did not activate mCAR. Real-time Q-PCR analysis in wild-type C57BL/6 mice revealed that OAT induces the hepatic mRNA expression of the following CAR target genes: Cyp2b10, Cyp2c29, Cyp3a11, Ugt1a1, Mrp4, Mrp2 and c-Myc. CAR-null (Car−/−) mice showed no increased expression of these genes following OAT treatment, demonstrating that CAR is required for their OAT dependent induction. The OAT-induced CAR-dependent increase of Cyp2b10 and c-Myc expression was confirmed by Western blotting. Immunohistochemistry analysis of wild-type and Car−/− livers showed that OAT did not acutely induce hepatocyte proliferation, but at much later time points showed an unexpected CAR-dependent proliferative response. These studies demonstrate that mCAR is an OAT xenosensor, and indicate that at least some of the biological effects of this compound are mediated by this nuclear receptor.

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Section: Introductionmentioning

confidence: 99%

Ortho-aminoazotoluene activates mouse constitutive androstane receptor (mCAR) and increases expression of mCAR target genes

Сметанина

Pakharukova

Kurinna

et al. 2011

Toxicology and Applied Pharmacology

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“…Cecal tumors detected in 19 of 60 A/He mice treated with OAT could be induced by this carcinogen [4]. However, later we detected similar tumors in elderly intact A/He mice (data not published).…”

Section: Resultsmentioning

confidence: 50%

“…In contrast to hepatic tumors most incident in mice, intestinal tumors are very rare [4,8]. Cecal tumors detected in 19 of 60 A/He mice treated with OAT could be induced by this carcinogen [4].…”

Section: Resultsmentioning

confidence: 97%

PT/Y Mice Are Sensitive to the Inhibitory Effect of o-Aminoazotoluene on Glucocorticoid Induction of Tyrosine Aminotransferase and Its Hepatocarcinogenic Effect

et al. 2015

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PT/Y mice used for studies of the effects of mutagens are characterized by the absence of spontaneous tumors of the liver, but often develop these tumors in response to chronic oaminoazotoluene treatment. The level of glucocorticoid induction of adaptive hepatic enzyme tyrosine aminotransferase decreases by more than 70% 24 h after acute injection of o-aminoazotoluene to these animals. These mice can serve as a model for studies of the relationship between the effect of carcinogens on the regulation of activity of adaptive hepatic enzymes and their capacity to induce the development of liver tumors.

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“…The authors suggested that in some mouse strains the colon is a target organ for OATinduced carcinogenesis. Indeed, in our paper published more than two decades ago (Kaledin et al, 1978) it was shown that under repeated administration OAT is carcinogenic for cecum of A/He mice. However, somewhat later we found that mice of this strain are predisposed to spontaneous development of the cecum tumors (Kaledin et al, 1984).…”

Section: Discussionmentioning

confidence: 95%

o-Aminoazotoluene does induce the enzymes of its own mutagenic activation in mouse liver

et al. 2005

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Carcinogenicity of orthoaminoazotoluene for the mouse intestines

Cited by 4 publications

References 0 publications

Ortho-aminoazotoluene activates mouse constitutive androstane receptor (mCAR) and increases expression of mCAR target genes

Ortho-aminoazotoluene activates mouse constitutive androstane receptor (mCAR) and increases expression of mCAR target genes

PT/Y Mice Are Sensitive to the Inhibitory Effect of o-Aminoazotoluene on Glucocorticoid Induction of Tyrosine Aminotransferase and Its Hepatocarcinogenic Effect

o-Aminoazotoluene does induce the enzymes of its own mutagenic activation in mouse liver

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