Effects of o-aminoazotoluene on liver regeneration and p53 activation in mice susceptible and resistant to hepatocarcinogenesis

Timofeeva, O. A.; Eremeev, Artem V.; Goloshchapov, Andrey; Kalashnikova, Eugenia; Ilnitskaya, S. I.; Setkov, N. A.; Кобзев, В. Ф.; Buzard, Gregory S.; Филипенко, М. Л.; Каледин, В. И.; Меркулова, Т. И.

doi:10.1016/j.tox.2008.09.013

Cited by 8 publications

(5 citation statements)

References 47 publications

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“…In A/He mice (with moderate sensitivity to OAT hepatocarcinogenic effect), TAT induction reduced by 58% in response to OAT [9]. In SWR and DD mice, developing hepatic tumors in response to chronic OAT in about 100% cases [9], TAT induction was suppressed by almost 3 / 4 (70%) in response to an acute OAT injection. In PT/Y mice, also sensitive to OAT hepatocarcinogenic effect, the carcinogen virtually similarly (by 73.6±2.3%) suppressed the glucocorticoid induction of TAT.…”

Section: Resultsmentioning

confidence: 98%

“…Interestingly, the effects OAT on mice of different lines differ: the compounds strongly inhibits enzyme induction in DBA/2, DD/He, SWR mice and just slightly in AKR and CC57BR mice [6,7]; DBA/2, DD/He, and SWR mice are highly sensitive to the hepatocarcinogenic effect of OAT, while AKR and CC57BR are highly resistant to it [5,9]. It remains unclear whether the relationship between these parameters is obligate or just simulated because of the small size of the sample.…”

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confidence: 99%

“…Incidence of Liver Tumors in Male Mice of Different Lines after Chronic OAT Treatment and the Level of Glucocorticoid Induction of TAT in the Liver 24 h after a Single OAT Injection[5,9] Note. Induced TAT activity, % of the level in control mice.…”

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confidence: 99%

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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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Section: Resultsmentioning

confidence: 98%

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confidence: 99%

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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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“…AAB and OAT each exhibit in vitro mutagenic activity in the Ames test using Salmonella typhimurium strain TA 98 activated by liver enzymes, where such activity was suppressed by adding pentachlorophenol (PCP) and induced by adding 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) to the activating enzymes [80]. However, tumor multiplicity exhibited in tumorsusceptible mouse strains neonatally exposed to OAT was increased with PCP pretreatment but was reduced with TCCD metabolic-activation pretreatment; in contrast, PCP pretreatment was observed to inhibit AAB-induced carcinogenic activity in three strains of mice [81].…”

Section: Appendixmentioning

confidence: 99%

Biphasic hCAR Inhibition-Activation by Two Aminoazo Liver Carcinogens

Bogen¹

2018

Nuclear Receptor Research

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Detailed dose-response data recently archived by the National Center for Biotechnology Information (NCBI) identified 853 human CAR (hCAR) agonists by quantitative highthroughput screening (qHTS) assays applied to >9,000 chemicals tested at ≥14 concentrations using n = 3-48 replicates. By reexamining NCBI data on 746 agonists with replicate data sets each satisfying additional quality criteria, ∼95% had average values of agonist-specific Hill-model slopes estimated by NCBI that exceed 1 (i.e., exhibited an overall sublinear lowdose dose-response), and two unambiguously biphasic hCAR inhibitor-agonists were identified, 4-aminoazobenzene (n = 37) and ortho-aminoazotoluene (n = 3), both of which also cause rodent liver tumors. Although evidently rare among hCAR agonists, such biphasic responses add to evidence that nuclear receptors can exhibit complex patterns of low-dose response, consistent with previous observations and theoretical predictions for endpoints governed by ultrasensitive molecular switches. The pronounced biphasic hCAR response pattern observed for 4-aminoazobenzene is particularly noteworthy insofar as it was identified with statistical power that exceeds that of most if not all other receptor-mediated biphasic cellular responses to any single-chemical exposure reported to date.

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“…Later studies of the mechanism of carcinogenic activity of aminoazostains were carried out mainly on mono-and dimethyl derivatives of aminoazobenzene in rats, while OAT was used in just solitary studies. It exhibited slight hepatotoxic and clastogenic activities [11,12] and rather high mutagenic activity, manifesting in bacterial tests in vitro in the presence of microsomal and cytoplasmic hepatic enzymes [7,8]. The OAT mutagenic metabolites formed under the effects of enzymes from animals sensitive and resistant to its hepatocarcinogenic activity [13].…”

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confidence: 99%

Suppression of Sulfoconjugation Reduces the Protective Effect of Ortho-Aminoazotoluene on Hepatocarcinogenesis Induced by Diethylnitrosamine in Mice

et al. 2014

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The effects of ortho-aminoazotoluene on carcinogenic activity of diethylnitrosamine were studied in CBA and ICR mice. Injection of ortho-aminoazotoluene before and after diethylnitrosamine led to a significant reduction of its anticarcinogenic effect, judging from significantly lower level of liver tumors. Pentachlorophenol, inhibitor of sulfotransferase (catalyzing the terminal stage of ortho-aminoazotoluene metabolic activity), stimulated its carcinogenic effect on mouse liver. On the other hand, pentachlorophenol reduced the protective effect of ortho-aminoazotoluene on diethylnitrosamine-induced hepatocarcinogenesis in mice. Presumably, the carcinogenic and anticarcinogenic effects of ortho-aminoazotoluene were realized by its initial form or intermediate (non-sulfated) metabolites.

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Effects of o-aminoazotoluene on liver regeneration and p53 activation in mice susceptible and resistant to hepatocarcinogenesis

Cited by 8 publications

References 47 publications

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

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

Biphasic hCAR Inhibition-Activation by Two Aminoazo Liver Carcinogens

Suppression of Sulfoconjugation Reduces the Protective Effect of Ortho-Aminoazotoluene on Hepatocarcinogenesis Induced by Diethylnitrosamine in Mice

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