Collect. Czech. Chem. Commun.
2010, 75, 1229-1247
https://doi.org/10.1135/cccc2010077
Published online 2010-11-18 07:31:56
Rat liver microsomal metabolism of o-aminophenol and N-(2-methoxyphenyl)hydroxylamine, two metabolites of the environmental pollutant and carcinogen o-anisidine in humans
Karel Naimana, Petr Hodeka, Jiří Liberdaa, Heinz H. Schmeiserb, Eva Freic and Marie Stiborováa,*
a Department of Biochemistry, Faculty of Natural Sciences, Charles University in Prague, Albertov 2030, 128 43 Prague 2, Czech Republic
b Research Group Genetic Alteration in Carcinogenesis, National Center for Tumour Diseases, German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany
c Division of Preventive Oncology, National Center for Tumour Diseases, German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany
Abstract
o-Aminophenol and N-(2-methoxyphenyl)hydroxylamine are human metabolites of the industrial and environmental pollutant and bladder carcinogen 2-methoxyaniline (o-anisidine). The latter one is also a human metabolite of another pollutant and bladder carcinogen, 2-methoxynitrobenzene (o-nitroanisole). Here, we investigated the ability of rat hepatic micro- somes to metabolize these metabolites. N-(2-methoxyphenyl)hydroxylamine is metabolized by rat hepatic microsomes to o-aminophenol and predominantly o-anisidine, the parent carcinogen from which N-(2-methoxyphenyl)hydroxylamine is formed. In addition, two N-(2-methoxyphenyl)hydroxylamine metabolites, whose exact structures have not been identified as yet, were generated. On the contrary, no metabolites were found to be formed from o-aminophenol by rat hepatic microsomes. Whereas N-(2-methoxyphenyl)hydroxylamine is responsible for formation of three deoxyguanosine adducts in DNA, o-aminophenol seems to be a detoxication metabolite of N-(2-methoxyphenyl)hydroxylamine and/or a parental carcinogen, o-anisidine; no o-aminophenol-derived DNA adducts were found after its reaction with microsomal cytochromes P450 and peroxidases.
Keywords: o-Anisidine; N-(2-Methoxyphenyl)hydroxylamine; o-Aminophenol; Metabolism; Activation and detoxification.
References: 34 live references.
