Genotoxicity of o-aminoazotoluene (AAT) determined by the Ames test, the in vitro chromosomal aberration test, and the transgenic mouse gene mutation assay

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

“…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].…”

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

“…On specially created transgenic Muta mice the authors observed how many mutations were caused by OAT in this or that organ of animals in vivo. In a dose of 300 mg/kg (higher than a single dose commonly used for tumor induction) OAT virtually did not increase the incidence of mutations in any of the studied organs (including the liver and lungs -targets for its carcinogenic activity), while in a dose of 600 mg/kg (80% LD 50 ) it increased the incidence of mutations in the liver and even in the urinary bladder and kidneys, in which it had never induced tumors [8].…”

“…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].…”

“…One of the latest attempts at detecting the relationship between the carcinogenic and mutagenic activities of OAT was made by the Japanese scientists [8]. On specially created transgenic Muta mice the authors observed how many mutations were caused by OAT in this or that organ of animals in vivo.…”

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

“…It has been previously shown that the hepatic S9-fraction from rats treated with o-aminoazotoluene devoted to studies of its genotoxicity were published in "Mutation Research" last year (Ohsava et al, 2000;Kohara et al, 2001). OAT has been evaluated by the International Agency for Research on Cancer (IARC) as a possible (Class 2B) human carcinogen (IARC, 1975).…”